Cytokines' Role in Transfusion Reactions

Blood transfusion has evolved to a sophisticated medical treatment. Over the past 30 years
or so, improvements in blood collection and storage materials changed blood transfusion
from a relatively nonspecific treatment to a therapy treating specific hematopoietic and
coagulation disorders with blood components proven to abate the disorder.

In many medical arenas, transfusions have declined in favor of other therapies. However,
therapies for many diseases still require blood transfusion.

Recognition of ABO groups was the first step in increasing transfusion safety. In the ensuing
years, compatibility testing increased the safety of the transfusion to the recipient. Despite
the overall improvement in transfusion safety, one area--transfusion reaction--still presents
risk to the recipient.

The causes for the majority of life-threatening transfusion reactions are well understood and
most reactions themselves are preventable. Well-established transfusion protocols ensure a
successful final outcome. One of the best examples of this is the acute hemolytic transfusion
reaction, which is most often caused by ABO incompatibility. Careful patient, patient/sample
and blood/recipient identification, as well as laboratory testing, prevent almost all such
transfusion reactions.

Some Reactions Unpredictable

Other transfusion reactions are more

difficult to predict and prevent because
their causes are not fully understood.

Febrile transfusion reactions are an

example. In most cases, these are caused
by alloimmunization to leukocyte antigens.
Reaction in these recipients is prevented
by leukocyte-reducing the blood
components prior to transfusion. There
remains a significant population of
transfusion recipients who lack leukocyte
antibodies but still suffer reactions to
leukocyte-reduced blood components. In
these individuals, the reaction must be
caused by other factors. Recent studies
indicate cytokines may be one potential cause for these recipients' continued reactions.1-
4
Studies also indicate cytokines may play roles in hemolytic transfusion reactions.1-4

What is a Cytokine?

Cytokines are polypeptide, hormone-like substances secreted by macrophages,

lymphocytes and endothelial cells. The term cytokine is also used to refer to molecular
products of immune system cells or substances that act upon those cells.

Cytokines fall into three basic functional groups: hematopoietic cell growth and differentiation
stimulators, natural inflammation mediators and specific immune response regulators1,2,4 (see
Table 1). Some cytokines' effects may fall into more than one category.

Cytokines in HTR

The role of cytokines in hemolytic transfusion reactions (HTR) is not well characterized. 1
Cytokines with known involvement include interleukin-1 (IL-1), tumor necrosis factor (TNF),
interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein (MCP), and
interleukin-1 receptor antagonist (IL-1ra).1-4 The activities of these substances and others