Drugs

Glucocorticoids

Prednisone
Prednisolone

Mechanism

Effects/ Uses

Side effects

GC binds to GC-responsive element, modify the

transcription of genes

Reduce peripheral lymphocytes;

Inhibit T-cell proliferation and immunity;
Downregulate cytokine production
Used in organ transplant/ HSCT (prevent GVHD)

Immunodeficiency
DM (hyperglycaemia)
Osteoporosis (disrupt Ca)
Muscle breakdown
Mood swing
Cushings syndrome

Calcineurin induces different transcription factors

(NFATs) that are important in the transcription of IL-2
genes. IL-2 activates T-helper lymphocytes and induces
the production of other cytokines.

CsA forms a complex with cytophilin

FK506 forms a complex with FKBP
complex inhibits calcineurin

Renal dysfunction
Bone marrow toxicity
Hypertrichosis
Gingival hyperplasia HT, HG, GI

Bind to FKBP and inhibit mTOR, block the progression of

activated T-cells from G1 to S phase of cell cycle

Inhibit mitogenic response to IL-2.

Inhibit B-cell proliferation and antibody production.

Hyperlipidemia
Myelosuppression
Thrombocytopenia
Nephrotoxicity

Prevent clonal expansion of both B and T-cells

Myelosuppression
GI toxicity

Calcineurin inhibitors
Cyclosporine (CsA)
Tacrolimus (FK506)
Proliferation-signal inhibitors
Sirolimus
Everolimus

Antimetabolites and cytotoxic drugs

Azathioprine (AZA)
Inhibit purine synthesis
Inhibit IMPD the enzyme necessary for de novo purine
Mycophenolate mofetil (MMF)
synthesis (lymphocyte has no salvage pathway)
Leflunomide
Inhibit pyrimidine synthesis
Cyclophosphamide
Alkylating agent
Methotrexate
Antifolate agent
Chlorambucil
Alkylating agent
Antibodies (humanised murine Ab)
Polyclonal antibodies bind to T-cells
Antithymocyte globulin (ATG)
cause lysis and mask lymphocyte receptors
Muromonab-CD3
IL-2 antagonists
Basiliximab
Daclizumab
Anti-TNFa agents
Infliximab
Adalimumab
Etanercept

Abatacept
Immunomodulatory agents
Filgrastim (G-CSF)
Sargramostim (GM-CSF)
IFN-g
Aldesleukin

Avoid humoral and CMI response

Directed against CD3 antigen of T cells

Deplete circulating T cells within minutes

Prevent GVHD in HSCT and transplant rejection

Bind to IL-2 receptors on T cells and inactivate IL-2

mediated cell activation and proliferation

Suppress T-cells
Used for prophylaxis in organ transplant

Monoclonal antibodies catch soluble TNF-a, preventing

it from activating TNF receptors
Recombinant form of soluble TNFa receptors, competing
against cell surface TNFa receptors
Bind to CD80 and CD86 on APC, preventing binding to
CD28 on T-cells
(i.e. compete against T-cells for APC cell surface
ligands)

Infliximab: used in Crohns disease

Adalimumab: used in RA

Anaphylaxis
Serum sickness reactions
Fever, vomiting, headache
Pulmonary oedema
Anaphylaxis
Well-tolerated, no side effects

Used in RA
Risk of infections
Used in severe RA

Accelerate bone marrow recovery

Activate phagocytosis by increasing synthesis of TNF
Promote proliferation and differentiation of lymphocytes into cytotoxic cells, activate NK cells