[The interferons: pharmacology, mechanism of action, tolerance and side effects]

Abstract

Background: Interferons are a recombinant form of endogenous interferon. By inducing the release of intracellular enzymes such as 2'5' oligoadenylate synthetase and double stranded RNA dependent protein kinase, the drug causes degradation of viral messenger RNA and inhibits protein synthesis.

Main points: Interferons are cytokines efficient in the treatment of infections diseases. Three main types are described as alpha, beta and gamma depending on their antigenic specificity. They have antiviral activity, antiproliferative and immunomodulation properties in response to a viral infection or other enzyme inducers. Furthermore, they increase expression of major histo-compatible complex antigens, increase natural killer and cytotoxic T cell activity, cytokine induction and production of endogenous interferon. Adverse effects frequently occur but are generally wild and reversible at current dosages. The pharmacokinetics of interferons have been fairly well described. The decline in serum concentrations is rapid after intravenous administration. The volume of distribution approximates 20-60% of bodyweight. Terminal elimination half lives range from 4-16 hrs, 1-2 hrs and 25-35 min for alpha, beta, gamma respectively. Intra-muscular and subcutaneous administration of interferons alpha and bêta results in protracted but fairly good absorption > 80% for interferon alpha to 70% for interferon gamma. Pegylated interferon safety and pharmacodynamic profiles were comparable. Pegylated interferon demonstrated delayed clearance compared with non-pegylated interferon, consistent with once-weekly administration. The severity of adverse effects is dose dependent. Most patients treated have an influenza like syndrome within 2-8 hrs of drug administration. Other effects such as fatigue, lethargy, anorexia are usually dose limiting. Neuropsychiatric reactions may also become dose limiting. Interferon induced the formation of serum neutralizing antibodies in approximately 10-20% of treated patients.

Perspectives: The development of pegylated forms, a greater understanding of action mechanisms, and the combination with other therapies should reinforce the place of interferons in the therapeutic arsenal.