Inflammatory cytokines in animal health and disease.

Inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6 and IL-8, are rapidly induced early in a disease or injury process. They mediate and modulate myriad healing processes but, if overexpressed, may exacerbate the severity of a disease condition. In order to test this concept and to establish a foundation for the role of inflammatory cytokines in the pathogenesis of gram-negative bacterial infections in the respiratory tract of animals, the patterns of inflammatory cytokine expression were determined in experimental porcine pleuropneumonia. We observed that IL-1 and IL-6, but not TNF, were rapidly and dramatically elevated in the lavage fluid of the lung within 24 h of infection. The increased levels of IL-1 might contribute to increased severity of disease, but elevated IL-6 levels were consistent with a protective acute phase response. Additional studies were performed to examine the hypothesis that IL-4 expression later in infection might be involved in turning off the inflammatory response and promoting an antigen-specific humoral immune response. Interleukin-4 efficiently suppressed inflammatory cytokine production in alveolar macrophages. Its expression was induced in peripheral blood mononuclear cells by TNF, IL-4, and by reexposure to a specific antigen. To obtain the maximum amount of information on the role of inflammatory cytokines in animals of veterinary significance it will be useful to perform studies in species such that evolutionary relatedness will allow widespread application of the findings. Furthermore, the variety of molecules involved in inflammatory cytokine regulation will require much more extensive investigations of the relevant enzymes, inhibitors and receptors in veterinary species. Finally, the complexity and redundancy of immune defenses in animals mean that attempts to modulate health status through manipulation of inflammatory cytokines must be performed with caution and that a multiplicity of processes will be affected.