Immunomodulators in Bacterial and Fungal Infections: A Review of Their Therapeutic Potential

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Despite the development of new and powerful antimicrobial drugs, the therapy of severe bacterial and fungal infections remains a problem in immunocompromised patients. In these patients, defective host defence mechanisms preclude adequate clearance of micro-organisms, and alternative ways are being sought to restore host resistance.

Recently, a variety of cytokines and growth factors have been isolated that play an important regulatory role in host defence against infection. Administration of these factors to experimental animals has been shown to be beneficial in various models of infection.

Injection of a single dose of interleukin-1 or tumour necrosis factor-α protects animals from infection with a variety of micro-organisms, including Gram negative bacteria, protozoa and fungi. The mechanism by which these cytokines induce their beneficial effects has not yet been elucidated. However, the extensive experimental data suggest that induction of humoral factors and modulation of cytokine receptor expression may be important in this respect.

For other cytokines, such as interleukin-12 and interferon-γ, protection against facultative intracellular micro-organisms is probably mediated by induction of cellular immunity and macrophage activation. However, other mechanisms, such as activation of polymorphonuclear leucocytes and interaction with other types of cells, also appear to play a role in interferon-γ-induced protection.

Some of the cytokines, such as interferon-γ, interleukin-2 and the colonystimulating factors, are currently being used in the therapy of infection in humans. Whether interleukin-1 or tumour necrosis factor-α can be used for treatment of infections needs careful investigation because of their potential adverse effects.

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