Overview of biologic response modifiers in infectious disease.

The conventional treatment of infectious agents is increasingly encountering antimicrobial resistance. This resistance has led to an intense search for novel treatment modalities for infectious diseases. Elucidation of the mechanisms underlying the inhibitory activity of chemokines has been instrumental in the rational design of anti-human immunodeficiency virus chemokine drugs.

Novel concepts for anti-infective activity of cytokines, chemokines and diverse agents.

Access to an array of cytokines and synthetic immunomodulators represents a significant milestone in the development of effective therapies for infectious diseases. Several recombinant human cytokines, including interferons and colony-stimulating factors, are licensed and being widely used in clinical practice in patients. The identification of the essential role of coreceptors for the entry of HIV into the host cell has focused attention on chemokines as important targets for pharmacological intervention and several new compounds possessing therapeutic potential as inhibitors of chemokine receptors have been advocated.

Low dose oral combination chemoprophylaxis with oseltamivir and amantadine for influenza A virus infections in mice.

In the present study, the effect of combining anti-influenza drugs active at different steps of the influenza virus replication cycle, oseltamivir as a neuraminidase (NA) inhibitor and amantadine targeting M2 protein, was investigated in vivo by oral administration in a mouse model of aerosol influenza virus infection and in vitro in MDCK cells. In mice, doses of oseltamivir and amantadine providing 50-60% survival against A/Hongkong/1/68 (H3N2) or A/PR/8/34 (H1N1) were capable of conferring complete protection when used simultaneously, suggesting that increased inhibition of influenza virus replication by combining oseltamivir and amantadine in vitro translates into protection from lethal infection of mice. The combination of amantadine with oseltamivir required 15-fold less oseltamivir than monotherapy to confer complete protection against lethal aerosol influenza virus infection.

Natural products and synthetic compounds as immunomodulators.

Research on immunomodulation by natural products or synthetic derivatives is of key interest for anti-infective therapy for a number of reasons. Many plant remedies well-known in traditional medicine or refined natural products in clinical use exert their anti-infective effects not only (if at all) by directly affecting the pathogen. At least part of their effect is indirect, by stimulating natural and adaptive defense mechanisms of the host.