Table 1.

Mechanism of action and side effects of immunomodulatory agents.

Immunomodulators	Category	Example	Mechanism	Main side effects	Reference
Immunosuppressant	Inhibitors of lymphocyte gene expression.	Glucocorticoids	Decreased leukocytes extravasation. Reduce pro-inflammatory cytokines expression.	Growth retardation in children, bone necrosis, osteopenia, hyperglycemia, and hypertension.	Golan (2008), Jain (2008)
	Inhibitors of lymphocyte signaling	Cyclosporine	Antigen-triggered signal transduction constrain in T lymphocytes. Reduce expression of lymphokines and anti-apoptotic proteins.	Renal dysfunction, gum hyperplasia, hyperuricemia, hyper-cholesterolemia, diabetogenic.	Jain (2008), Tortora and Derrickson (2008)
		Tacrolimus	Inhibits T-cell activation by inhibiting calcineurin.	Nephrotoxicity, neurotoxicity hypertension, hyperkalemia, hyperglycemia.	Singhal (2007), Sengupta (2009)
		Sirolimus	Inhibit activation and proliferation of T-lymphocyte. Down regulate T-cell growth factor receptor and IL-2.	Level of serum cholesterol and triglycerides increase. Impaired renal functions, prolong delayed graft function.	Katzung and Trevor (2009), Gilman’s (2008)
	Cytotoxic agents	Azathioprine, azathioprine sodium	Inhibit de novo synthesis of purine which leads to inhibit proliferation of lymphocytes.	Leukopenia, thrombocytopenia, hepatotoxicity, alopecia, GI toxicity, pancreatitis.	Katzung and Trevor (2009)
		Mycophenolatmofetil	Inhibit de novo synthesis of guanine by inhibiting inosine monophosphate dehydrogenase.	Leukopenia, diarrhea, vomiting, sepsis associated with cytomegalovirus.	Rang and Dale (2007), Richard and Pamela (2009)
	Alkylating agent	Cyclophosphamide	Prevent the cell division and protein synthesis by cross linking in the strands of DNA.	Pancytopenia and hemorrhagic cystitis, graft versus–host disease syndrome, cardiac toxicity, electrolyte disturbances	Mythili et al. (2004)
	Cytokine inhibitors	Etanercept, infliximab, adalimumab, anakinra, daclizumab, basiliximab	Bind with tumor necrosis factor-alpha and inhibit TNFα to bind with TNFα receptors.	Reactivation of tuberculosis, psoriasis, invasive fungal infections, hypersensitivity, and anaphylaxis.	Keane et al. (2001), Baudouin et al. (2003), Bartelds et al. (2011)
	Antibodies against specific immune cell molecules	Antithymocyte globulin	Reduce circulating lymphocytes by inducing cytotoxicity. To inhibit lymphocytes functions, it binds with cell surface molecules which regulate cell functions.	Fever, chills, hypotension, serum sickness, glomerulonephritis, leukopenia, and thrombocytopenia.	Hansel et al. (2010)
		Muromunab	Prevent subsequent antigen recognition by causing internalization of the T-cell receptor.	Cytokine release syndrome, high fever, chills/rigor, myalgias, arthralgias, aseptic meningitis, cardiovascular collapse, cardiac arrest.	Sgro (1995), Katzung and Trevor (2009), Liu and Li (2014)
	Intercellular adhesion molecules inhibitors	Efalizumab	Inhibit T-cell adhesion and trafficking by inhibiting LFA-1-ICAM interaction.	Bacterial sepsis, viral meningitis, invasive fungal disease, and progressive multifocal leukoencephalopathy.	Berger et al. (2009)
Immunostimu-lants	Imidazothiazole derivative	Levamisole	Repair the suppressed immune function of B and T lymphocytes, monocytes, and macrophages.	Flu-like symptoms, allergic manifestation, nausea, and muscle pain.	Auffenberg et al. (2013)
	Recombinant cytokines	Aldesleukin, interferon alpha, interferon gamma.	Inhibit cell proliferation and enhance immune cells activities such as increased macrophages phagocytosis and T lymphocytes cytotoxicity.	Hypotension, arrhythmias, cardiomyopathy myocardial infarction, GI distress, and anorexia.	Katzung and Trevor (2009), Strayer and Carter (2012)
	Hormonal analog	Isoprinosine	Enhance cytokines (i.e., IL-1, IL-2, and IFN-γ) production. It induces lymphocytes proliferation.	CNS depressant, transient nausea, and increase uric acid level in serum and urine.	Campoli-Richards et al. (1986), Parnham and Nijkamp (2005)