CYTOKINE IMMUNOMODULATION OF INFECTIOUS DISEASES IN HANDBOOK OF IMMUNE MODULATING AGENTS

Authors: Urban, Joseph; SHEA-DONOHUE, T - USUHS; GAUSE, W - USUHS; FINKELMAN, F - UNIV OF CINCINNATI

Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 4/10/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: The set of immune system regulatory molecules, called cytokines, that are produced in response to an infectious agent is critical to the survival and well-being of the host. However, excess or inappropropriate production of cytokines can have the opposite effect and enhance disease and facilitate secondary infection. In addition, cytokines are often induced as patterned responses to different classes of infectious agents; protozoan parasites and microbes evoke a type 1 response while worm parasites induce a type 2 response. Cytokines have the additional property of being counterregulatory. Thus, effective regulation of cytokine responses can control infection, reduce tissue destruction, and limit secondary infections that decrease the general health and productivity of infected livestock. Strategies to control excessive or inappropriate cytokine responses to infection can provide tools to improve performance and lower the cost of production. Future development of vaccines to limit infection and recombinant cytokines to down-regulate excess production of internal modulators of immunity will be useful agents for producers and veterinarians to implement effective controls.

Technical Abstract: Polarized CD4+ T-cell responses that express a distinct pattern of type 1 cytokines (IFN-g, IL-2, LT) or type 2 cytokines (IL-4, IL-5, IL-9, IL-10, IL-13) are often sufficient to neutralize the infectivity of distinct classes of pathogens and/or their capacity to cause disease. Homeostasis is maintained by inherent counter- regulatory properties and interactions of these cytokines across the response spectrum. Parasite interactions with the host that minimize or divert protective responses can provide an avenue for infection and convert acute disease to more chronic forms. Alternatively, positive feed-back induction of high concentrations of protective cytokines can limit superinfection by homologous parasites and reduce competing heterologous infections. Furthermore, unregulated production of cytokines can enhance disease through unlimited growth of the infecting organism, opportunistic secondary infection, or exaggerated immunopathological responses. Modulation of host cytokine expression is normally dependent on the nature of unique molecules expressed by the parasite, on parasite dose, and on host genetics which leads ultimately to effects that are either appropriate to control infection, that maintain chronic or dormant infection, or that inappropriately enhance disease.