Fish & Shellfish Immunology (2008) 25, 191e201

available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/fsi

REVIEW

Biological effects of bacterial lipopolysaccharide

(endotoxin) in fish: A review
P. Swain*, S.K. Nayak, P.K. Nanda, S. Dash

Fish Health Management Division, Central Institute of Freshwater Aquaculture,

Kausalyaganga, Bhubaneswar 751 002, Orissa, India

Received 24 December 2007; revised 2 April 2008; accepted 18 April 2008

Available online 26 April 2008

KEYWORDS Abstract Bacterial lipopolysaccharides (LPS), also termed endotoxins, considered to be

Biological effects; a major virulence factor, are responsible for the lethal effects and clinical manifestations of
Endotoxin; diseases in humans and animals. Higher animals are extremely sensitive to endotoxin even
Fish; at low doses but lower vertebrates like fish are often resistant to endotoxic shock. Toll-like re-
Gram-negative ceptor (TLR)-4 is mainly involved in the activation of the immune system by LPS through the
bacteria; specific recognition of its endotoxin (Lipid A) moiety. Although several Toll-like receptors
Lipopolysaccharide are present in fish, those molecules specifically involved in TLR-4 mediated endotoxin
recognition have not been fully established in different fish species. Despite this, LPS has
the potency to express cytokines, acute-phase proteins and also exerts immunological, path-
ological, physiological, immuno-endocrinological and neuro-immunological effects in several
fish species. The immunostimulating effects of endotoxin by triggering various immune para-
meters such as T and B lymphocytes, macrophages, and complement systems have been estab-
lished in teleosts. This article reviews the multiple biological effects of endotoxin which will
further strengthen the knowledge among researchers on various aspects of endotoxin in lower
vertebrates, particularly in the piscine system.
ª 2008 Elsevier Ltd. All rights reserved.

Introduction the host resulting in strong innate inflammatory

Endotoxins, the non-secreted cell membrane inherent
toxins, are capable of producing toxic manifestations in
* Corresponding author. Tel.: þ91 943 723 1099; fax: þ91 674 246
5407.
E-mail address: pswainy2k@yahoo.co.in (P. Swain).
responses. They are considered to be the major virulence
factor for several Gram-negative bacteria, and are
responsible for the lethal effects and clinical manifesta-
tions of diseases in humans and animals [1e4]. The effects
of Gram-negative bacterial infections and/or endotoxin in
chronic cases are often deleterious as compared to acute
cases [5].

1050-4648/$ - see front matter ª 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.fsi.2008.04.009
192
Endotoxins are the complex lipopolysaccharide compo-
nents of the outer cell wall membrane of Gram-negative
bacteria. They are usually large molecular weight sub-
stances with unique chemical structure, consisting of three
regions, i.e., an outer polysaccharide region (commonly
known as ‘O’ antigen, a linear or branched component of
oligosaccharide residues), a unique polysaccharide core
region (consisting of short chain sugars), and an inner fatty
acid rich region (i.e., Lipid A containing diglucosamine unit
with long-chain fatty acids) (Fig. 1). The polysaccharide
moiety is mainly responsible for serological specificity while
the Lipid A moiety determines biological functions [6e8].
The Lipid A components are found to be uniform in differ-
ent Gram-negative bacteria, but their potency and spec-
trum of action differ from each other [9].
The prototypical name of endotoxin is lipopolysaccha-
ride (LPS), which is the cell wall component of most of the
Gram-negative bacteria. However, Gram-positive bacteria
like Listeria monocytogenes also possess endotoxin-like ac-
tivity [10]. Although the term ‘endotoxin’ is commonly
used, it is often referred to by synonymous terms like pyro-
gen, LPS, or biovin antigen [11]. In aquaculture, LPS is the
most commonly used terminology.
Higher animals are extremely sensitive to endotoxin
even at low doses but lower vertebrates such as frog and
fish are stated to be resistant to endotoxic shock [12].
However, endotoxin/LPS has been found many times to
be responsible for the pathogenicity of several bacterial
diseases, especially of Gram-negative origin, in fish [13].
Therefore, this review elucidates the basic mechanism
through which endotoxin interacts by manifesting multiple
biological effects in different fish species. This will further
strengthen the knowledge among researchers on various
aspects and mechanism of action of endotoxin in lower
vertebrates, particularly in fish.
Biological activity of endotoxin
Endotoxin can induce innumerable biological effects in all
living systems. No other natural product is known to elicit
such a great diversity of reaction as endotoxins do [11].
Common endotoxic effects include shock, pyrogenicity,
Figure 1 A typical lipopolysaccharide unit showing different
regions.
P. Swain et al.
hypotension, neutropenia, intravascular coagulation, hypo-
ferraemia, leucocytosis, leucopenia, sepsis and abortion
[14e21]. In a host it affects the cellular and humoral immu-
nity, carbohydrate and lipid metabolisms, and haematolog-
ical parameters. However, these physiological and
biochemical responses vary depending upon species and
the doses of the endotoxin. But at higher doses it could
be lethal to any animal.
In several aquatic species including fish, it exerts
multiple responses like immunological, pathological, phys-
iological, immuno-endocrinological and neuro-immunologi-
cal effects [22e34]. The common effects of endotoxin on
different fish species are summarized in Table 1. However,
many times these responses are qualitatively different in
lower vertebrates than in higher vertebrates. In mammals,
depletion of liver glycogen, depression of liver tryptophan
pyrrolase activity, instant decline in arterial pressure,
abrupt reduction of heart rate and severe hypotension are
common metabolic derangements observed in response to
endotoxin [47]. But fishes often do not respond in a similar
manner to mammals. For example, yearlings of coho
salmon (Oncorhynchus kisutch) and rainbow trout (Onco-
rhynchus mykiss), when injected with endotoxin, did not
show any cardiovascular response or effect on liver trypto-
phan pyrrolase activity except depletion of liver glycogen
level [47]. Similarly, in juveniles of salmon (Salmo salar),
significant decrease in the heart rate from 4th day onwards
after an initial increase in response to LPS was observed by
Eddy [38].
Endotoxicity and clinical effects
of endotoxin in fish
Endotoxic shock is a common problem in humans and
animals due to Gram-negative bacterial infection. Higher
vertebrates like cat, rabbit, guinea pig, dog, calf, swine
and human are very sensitive to endotoxic shock whereas
lower vertebrates like fish and frog are resistant to it
[47,48]. Fishes like O. kisutch and O. mykiss are reported
to be resistant to Escherichia coli and Aeromonas salmoni-
cida endotoxins for doses up to 80 mg kg1 body weight
[47]. Similarly, a tropical fish like Indian major carp, Labeo
rohita, is also found to resist endotoxin to a dose of 20 EU
per fish without showing any abnormality [33].
Endotoxin exerts several clinical signs and symptoms
such as hyperaemia or discolouration of mucus membrane,
hypotension, altered capillary refill time, acute disruption
of gastric, small and large intestine motility resulting in
decreased gastrointestinal sound, increased body temper-
ature, heart and respiratory rates, and dehydration in any
sensitive individual [49,50]. However, the clinical signs and
symptoms may vary depending upon the type, previous ex-
posure and dose of the toxin. In fish, upon administration
of endotoxin even at high doses, no clinical signs, changes
in body colouration, abnormalities and behavioural
changes could be recorded [33,47], although it could be
a potent anorexic agent for fish which can reduce the ap-
petite by influencing gene expression of appetite related
neuropeptide [51].
In an aquatic environment, fish are not only intimately
associated with Gram-negative bacteria but are also
 Biological effects of bacterial LPS (endotoxin) in fish
Table 1 In vivo effects of endotoxin in different fish species
Sl. No Fish LPS/Source Mode of administration Effects/Activity References
1 D. rerio E. coli Immersion Enhances the production of cytokines TNF-a, [34]
IL-1b
2 L. rohita E. coli Intraperitoneal @ Increases lysozyme, total globulin level, [33]
1 EU fish1 myeloperoxidase and respiratory burst
activities
L. rohita E. coli Intraperitoneal @ Decreases lysozyme, total globulin level, [33]
10 EU fish1 myeloperoxidase and respiratory burst
activities
3 P. flavescens LPS Intraperitoneal @ Increases cortisol level [35]
3 mg kg1 body weight
4 G. morhua A. salmonicida Bath/Feed treatment Increases survivability [36]
5 C. carpio LPS Immunization @ LPS 50/ Increases phagocytic activity, phagocytic index [37]
1250 mg fish1 of macrophages and Ig level
6 S. salar LPS Injection Decreases heart rate after 4 days [38]
7 S. salar LPS Bath (0.25% LPS þ 1% Increases lysozyme of head kidney, intestine, [39]
glucan) macrophages and polymorphonuclear cells
8 O. mossambicus E. coli (0111:B4) In vivo Increases plasma free fatty acid, cortisol level [25]
9 O. mossambicus E. coli (0111:B4) In vivo Releases adenocorticotropic hormone, a-MSH [24]
10 O. mossambicus E. coli Injection Increases CRH and a-MSH content. No change in [5]
cortisol level
11 C. carpio 10 mg ml-1 LPS þ 100 mg b- glucan Intraperitoneal Increases neutrophils, monocytes count [32]
0.25% LPS þ 1% glucan Oral No change in relative percentage of survival
100 mg ml-1 LPS þ 1000 mg b- glucan Bath No change in relative percentage of survival
LPS (10 mg) þb- glucan (100 mg) Intraperitoneal 100% relative percentage of survival
12 S. aurata E. coli Bath Increases anti protease activity containing [40]
protease inhibitors a 1 and 2, anti- plasmin, a2
macroglobulin. Enhances protection against
Photobacterium damsela
13 S. salar A. salmonicida Immunization Enhances specific antibody level [41]
14 O. mykiss A. salmonicida Intraperitoneal @ Increases antibody titre which persists up [42]
50 mg fish1 to 2e4 weeks
A. salmonicida þ Liposome Intraperitoneal @ Increases antibody titre which persists
50 mg fish1 up to 6e14 weeks
15 S. salar LPS In vivo Enhances phagocytosis, pinocytic activity, [43]
production of intracellular superoxidase anion
16 O. mykiss LPS In vivo Induces hypoferremic responses [44]
17 C. carpio A. hydrophila Dip immunization Enhances survivability. No specific antibody [45]
level
18 O. mykiss A. salmonicida/E. coli (055 B5) Intravascular Elevates cortisol level [46]
@ 25 mg kg1

193
194
tolerant to adverse effects of endotoxin. The initial
endotoxin responses like fever, inflammation, weight loss
and lethality can be mitigated, leading to its tolerance on
subsequent exposure. This tolerance could be a hyper-
responsiveness i.e., a primary stimulation by endotoxin
which leads to specific response(s) in an organism, and
subsequent stimulation may lead to only a minimal or no
response. Furthermore, low sensitivity monocyteemacro-
phage lineage cells to LPS indicate a lack of serum-borne
factors in fish which confer the sensitivity to LPS in
mammals, and this could be a reason for the resistance of
fish to endotoxic shock [52].
Uptake and localization of endotoxin
The uptake and subsequent localization of endotoxin in fish
is mostly accomplished by kidney, spleen, heart and gut.
However, the entire process depends upon the route of
administration of endotoxin. Lymphoid organs like kidney
and spleen trap any antigen for developing immunores-
ponse in fish. The anterior and posterior kidney and spleen
of fish usually take up the injected LPS. The sinusoidal
endothelial cells and sinusoidal macrophages, in addition to
splenic ellipsoid sheath cells and liver endothelial cells, are
involved in this process [53e56]. Intravenous administra-
tion of LPS can lead to its accumulation within a few min-
utes of injection in spleen, liver and kidney but within
24 h, its concentration is reduced in anterior and posterior
kidney in S. salar [53].
The endothelial cells and macrophages are the primary
endocytic cells in fish [43,57]. Besides this the endocardial
endothelial cells of heart are also capable of actively taking
up LPS in fish [58,59]. Seternes et al. [59] reported the
maximum accumulation of R type of Vibrio salmonicida
LPS, when administered intravenously, in heart followed
by spleen, liver, and intestine. The integument and gut
epithelial cells are involved in the uptake process of several
compounds such as laminaran (b-(1,3)-glucan) [60]. How-
ever, in the yolk sac larvae LPS is absorbed via gut lumen
and integument, followed by its transfer to kidney and
finally to the excretory duct lumen [30,61].
Recognition of endotoxin
The biological effects of endotoxin are highly dependent on
the receptors in the target cells which recognize it as
harmful and subsequently trigger the defence system. Toll-
like receptors (TLRs) recognize specific conserved regions
in bacteria [62] and among different TLRs, TLR-4 is criti-
cally involved in the aetiology of LPS-induced specific shock
in mammals [63,64]. The role of LPS is widely acknowl-
edged in the fish immunological response [58,65,66], and
the presence of TLR has now been well established in
different fishes [67e70]. However, the existence of TLR-4
along with the functional assessment of TLR-4, CD14 and
myeloid differentiation protein-2, which play a critical
role for LPS responsiveness in mammals, have not yet
been fully established in fish [41,52]. The fact that TLR-4
is mainly involved in the activation of the immune system
by LPS through the Lipid A moiety. Although in fish all the
TLR signalling elements are present, and few reports
P. Swain et al.
indicate the presence of TLR-4 in zebra fish (Danio rerio)
[71], its existence in a wide range of fish species as well
as those molecules specifically involved in TLR-4 mediated
endotoxin recognition has to be explored [72]. Despite
this, LPS has the potency to induce and express several
pro-inflammatory cytokines and acute-phase proteins
(APP) in different fishes [73e76].
Induction of acute-phase proteins
The response of mammals to LPS varies from simple to
intense reaction(s) involving massive immune activation
leading to profound neuro-endocrine and metabolic
responses, known as acute-phase response [77,78]. During
this phase, liver hepatocytes produce several proteins
although some are also produced by other cells like mono-
cytes, endothelial cells and fibroblasts [77,79]. These tissue
macrophages or monocytes are mainly responsible for initi-
ation of the acute-phase response [80]. The common APP
include complement components like C2, C3, C4, C5, C9,
C4b binding proteins and C1 inhibitors, coagulation
proteins, metal binding proteins, mannose binding lectins,
LPS binding proteins, fibrinogens, enzyme inhibitors, C-
reactive proteins and inflammatory proteins [77,79].
In mammals, during acute-phase responses, LPS binding
proteins (LBP) are produced by the liver which combines
with LPS to activate monocyteemacrophages and granulo-
cytes, LBP recognize by specific receptors on the mono-
cyteemacrophages and granulocytes via CD14 surface
receptor [81e86]. LPS bridges the binding of macrophages
by first binding with LPS, after which LBP, recognized by
specific CD14 receptors on monocyteemacrophages and
granulocytes, allow direct activation of phagocytes, B
and T lymphocytes, and other cells. Upon activation, these
cells (monocyte/macrophage) produce interleukin (IL)-1
and tumour necrosis factor (TNF)-a which trigger fibro-
blasts and endothelial cells resulting in the production of
several pro-inflammatory cytokines like IL-1, IL-6 and
TNF-a [87]. During endotoxic shock TNF-a, which is mainly
responsible for the cytotoxic effects of LPS, increases to
above the normal level [88,89]. The production of IL,
TNF and other cytokines in response to LPS has been
recorded in several fish species [73]. However, Huttenhuis
et al. [31] could not detect cytokines, inducible nitrous
oxide or APP expression in 3 weeks post-fertilized Cyprinus
carpio by oral treatment with LPS. Therefore, the
responses can vary depending upon age and type of fish
species.
Effects of endotoxin on fish immunity
Innate or natural immunity that recognizes the presence of
infectious agents for activation of adaptive immunity
[90e92] is usually stimulated by endotoxin in diverse
eukaryotic species including fish [42,49,77,93]. Like other
microbial compounds /products such as b-glucan and
dsRNA, LPS possesses certain conserved structural se-
quences that have profound effects on the immune system
of many animals. It can either enhance or suppress the im-
munity by affecting T cells, B cells, macrophages, and other
immune components in different animal species [94,95].
Biological effects of bacterial LPS (endotoxin) in fish
Endotoxin as stimulator of cellular immunity
Effect on leucocytes/lymphocytes
Endotoxin, in both in vitro and in vivo conditions, actively
stimulates the proliferation of fish B lymphocytes
[43,96e98]. The in vitro stimulation of leucocytes by LPS
in fishes like Paralichthys olivaceus, D. rerio and C. carpio
has been recorded [99e103]. Fish leucocytes, upon stimula-
tion with LPS, express the transcription of IL 1 gene [104].
However, the concentration of LPS varies depending upon
in vitro and in vivo assay conditions for stimulation of
leucocytes. In P. olivaceus, a higher dose of 500 mg ml1of
LPS has been recorded for the stimulation of peripheral
leucocytes [99,100]. Selvaraj et al. [101] recorded the
increase in total leucocyte count in C. carpio when admin-
istered with crude LPS of Aeromonas hydrophila isolated by
phenolechloroform method. Although there was significant
increase in neutrophils and monocytes even at a dose of
10 mg fish1 in the LPS-injected group, no marked change
in lymphocyte count with respect to dose (10, 50 and
100 mg fish1) and duration even up to the 17th day post
injection was recorded by them.
Effect on macrophages
Macrophages play a key role in primary immune responses
after pathogen invasion, causing inflammatory responses in
living systems. As endotoxin is a strong stimulator of
macrophages, it activates several signal transduction path-
ways to produce a variety of inflammatory cytokines in
humans and animals including fish [105,106]. However, ex-
cessive production of cytokines in response to LPS is often
lethal and regarded as the cause of septic shock [107]. On
the other hand, macrophages when exposed to sub-optimal
doses of LPS render tolerance to its subsequent exposure
and also manifest altered response(s) [106]. It can also
cause pronounced spreading of membrane and increase
organelle content of fish macrophages [43]. Table 2 shows
various in vitro effects of endotoxin on the macrophages
of different fishes. In vitro studies show the production of
IL-b and TNF by the macrophages of fish when stimulated
by LPS [74,108e110]. Phagocytosis and respiratory burst ac-
tivity as well as lysozyme, nitric oxide and prostaglandin E2
generation is also stated to be enhanced by LPS-stimulated
macrophages [39,104,111e113,117,118].
Neumann and Belosevic [118] reported a gradual in-
crease in the priming of macrophages in goldfish (Carassius
auratus) induced with LPS but recorded enhanced activity
when LPS was co-stimulated with macrophage-activating
Table 2 In vitro effects of macrophages in different fish species in response to endotoxin
Fish Effects
S. aurata, O. mykiss, D. labrax, C. carpio, Stimulates IL and TNF production; enhances
S. salar, C. auratus the expression of CD83 mRNA, serum amyloid A
levels; induces nitric oxide, prostaglandin,
lysozyme, cortisol production; increases
superoxide anion production and respiratory
burst activity
195
factors. On the other hand, Sarmento et al. [113] found
an initial increase in reacting oxygen intermediate by
LPS-stimulated macrophages followed by down-regulation
after 24 h of incubation.
LPS activates piscine macrophages to express lysozyme
through differentiation of macrophages as well as direct
activation of lysozyme gene transcript in both in vivo and in
vitro conditions. The expression of CD83 mRNA by different
cell types has been established [119] but its expression by
macrophages is controversial in mammals [41]. However,
Donate et al. [114] observed its high level of expression
by LPS-stimulated macrophages of gilthead sea bream
(Sparus aurata) and therefore, it could act as a marker
for activated mature myeloid cells in fish.
Similarly, cyclo-oxygenase prostaglandin, the enzyme
that is produced as a result of inflammatory responses, has
been reported to be increased significantly by C. auratus
macrophages stimulated by Salmonella typhimurium LPS
[104].
Endotoxin as stimulator of humoral immunity
Effect on antibody response
Endotoxin is considered to be a strong immunogen since
both the ‘O’ polysaccharide chain and the core region of
the molecule can act as antigenic determinant [120]. Fish
respond to LPS by sometimes producing antibody against
‘O’ side chains but not necessarily to the core region, and
vice-versa [120e122]. Unlike most of the protein and cellu-
lar antigens, it is a T-independent antigen [123,124] and
can directly stimulate B cells to induce antibody-mediated
immune response without activation of T cells or develop-
ment of immunological memories [125]. LPS not only
elevates the antibody level in various fishes like O. mykiss,
Salmo trutta and C. carpio [42,96,101,126,127], but also
often serves as a protective antigen in many fishes against
different pathogens [45,128,129]. Anderson et al. [130]
reported increased antibody production by dip immuniza-
tion with ‘O’ antigen of either Yersinia or Aeromonas
species. Many times, LPS in combination with other com-
pounds also trigger the immune system to produce a long-
lasting immune response. LPS pre-coated with bovine
serum albumin or oleic acid can give better protection
compared to the unmodified LPS [42,131]. Bogwald et al.
[131] found that particulate LPS from V. salmonicida and
Vibrio anguillarum serotype 01 failed to protect S. salar.
But V. anguillarum serotype 02 LPS gave a high protection
whereas the LPS-protein complex surface layer antigen
from V. salmonicida resulted in better protection. Similarly,
References
[74,98,104,106,
108e116]
196
Nakhla et al. [42] reported elevated antibody level in
O. mykiss against LPS of A. salmonicida incorporated with
liposome for a prolonged period up to 6e14 weeks as com-
pared to 2e4 weeks when injected without liposome.
Effect on complement and other activities
Complement system, which plays an essential role in
altering the host immune response in the presence of
potential pathogens, can be activated either by classical
or alternative pathways depending upon the smooth or
rough type of LPS. In teleost fish, activated complement
component C3 can lyse and clear microbes by covalently
binding to the microbial surface [132e135]. In fish, the an-
tibody independent alternative pathway has been directly
activated by LPS [136,137].
Haemagglutination is often reported to be a common
function of polysaccharide moiety of LPS. Since cell-
mediated haemagglutinating activity is related to bacterial
adhesion, LPS is believed to be an adhesin. Alam et al. [138]
also reported haemagglutinating activity of LPS from differ-
ent human enteropathogenic pathogens. However, in fish
haemolytic activity is not reported to be greatly affected
by endotoxin [33,139].
Immunostimulating effects
There are several reports confirming the immunogenic
nature of LPS, especially at low quantities in different
fish species [22,29,32,96,140,141]. It can trigger various
immune components in fish and enhance their survivability
as well. Fish larvae when treated with LPS exhibited signif-
icantly high anti-protease activity and total globulin level
[40]. Iliev et al. [72] found that immuno-modulatory
activity of LPS is inversely correlated with its water dispers-
ing ability. They have recorded weak induction of TNF-2 in
monocyteemacrophage lineage cells of O. mykiss by a high
dose of water-dispersible ultrapure LPS of E. coli (0111: B4)
compared to high induction of TNF-2 by the weak water-
dispersible LPS of E. coli (K12 msb B mutant). Many times,
better protection against pathogens is also achieved by
immunizing the fish with LPS compared to whole-cell bacte-
ria [45,101]. Selvaraj et al. [101] reported enhanced immu-
nity and survivability by immunizing the C. carpio with
A. hydrophila LPS. Similarly, Baba et al. [128] recorded
high survivability in C. carpio by dip immunizing the crude
A. hydrophila LPS. However, they failed to detect specific
antibody and believed there was involvement of cellular
immunity in protection.
Other effects of endotoxin in fish
Effect on corticosteroid responses
The immune cells of different animals respond more or less
in a similar manner to produce various hormones and
neuropeptides [142]. Under stress conditions, the immune
system in fish is adversely affected due to alteration of
different immunological and other metabolic responses
[143,144]. Under these conditions, cortisol level often
increases in the piscine system and elevation of cortisol in
P. Swain et al.
response to LPS has been recorded in Salvelinus fontinalis,
Oreochromis mossambicus, Perca flavescens and O. mykiss
under both in vivo and in vitro conditions [35,46].
Among different stress conditions, the rearing density
could also affect the severity of corticosteroid responses.
However under high stocking, fish could respond differently
to LPS treatment. Haukenes and Barton [35] reported
a significantly lower cortisol level when P. flavescens
were injected with LPS at 3 mg kg1 body weight at high
rearing density for 14 days than at low rearing density for
the same duration. Although cortisol can modulate tran-
scriptional responses of piscine macrophages in response
to LPS, its action is believed to be more complex than
simply the antagonism of LPS to induce transcriptional
responses [145].
Endotoxin is often found to modify the hypothalamo-
pituitary-adrenal axis and its involvement in immune
endocrine interactions has been reported in many fishes
[25,35,146]. In vitro administration of LPS to the pituitary
lobes inhibits the release of pituitary adrenocorticotropic
hormone as well as a-melanocyte stimulating hormone
(a-MSH). However, in juveniles of O. mossambicus
(4e5 weeks), corticotropin-releasing hormone and a-MSH
were increased in response to LPS [30].
In mammals, various cytokines and other immune factors
produced in response to endotoxin can affect the repro-
ductive system. Although in fish administration of LPS can
lead to ovarian apoptosis, very few attempts are being
made to study its effect on the reproduction of fish.
MacKenzie et al. [147] reported a marked increase in apo-
ptotic cell nuclei in the follicular layer with increase in
the expression of positive apoptosis mediator-like zipper-
interacting protein kinase in S. fontinalis within 24 h of
LPS administration. However, they could not report the in-
hibition of the production of ovarian steroid, oocyte matu-
ration, and follicular contraction by LPS.
LPS administration can also cause a marked decrease in
expression of genes involved in metabolism and mitochon-
drial biogenesis in fish, as reports indicate that in vivo
exposure to LPS damages mitochondrial DNA, and interferes
with mitochondrial transcription and oxidative phosphory-
lation in other systems [148]. Therefore, LPS could depress
cellular metabolism and energy production by attenuating
the expression of key genes involved in basic cellular
functions in fish.
Future research needs
The research on endotoxins is of paramount importance in
human and animal sciences due to their multiple biological
effects including shock. To date, no systematic attempts
have been made to study the toxicity and other activities of
LPS in different fish with respect to their habit and habitat.
The physical organization of LPS also plays an important
role in determining its biological activities depending upon
strains, methods of cultivation, extraction procedures, etc.
Such type of study would certainly give a new dimension in
understanding its effects in different fish species. Further-
more, adequate knowledge is required to know the role of
endotoxin and its adverse consequences such as severe
cytokine-induced shock, inflammation, and immunosup-
pressive effects with respect to dose and duration in
Biological effects of bacterial LPS (endotoxin) in fish
different fish species. Several questions are therefore
needing to be answered in order to understand the
basic mechanism of endotoxin recognition, and the
molecular receptors that regulate its activity and tolerance,
in fish.
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