INFLAMMATORY CYTOKINES IN ANIMAL HEALTH AND DISEASE

Inflammatory cytokines, including tumor necrosis factor (TNF), interle ukin-1 (IL-1), IL-6 and IL-8, are rapidly induced early in a disease o r injury process. They mediate and modulate myriad healing processes b ut, if overexpressed, may exacerbate the severity of a disease conditi on. In order to test this concept and to establish a foundation for th e 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 p orcine pleuropneumonia. We observed that IL-1 and IL-6, but not TNF, w ere rapidly and dramatically elevated in the lavage fluid of the lung within 24 h of infection. The increased levels of IL-I might contribut e to increased severity of disease, but elevated IL-6 levels were cons istent with a protective acute phase response. Additional studies were performed to examine the hypothesis that IL-4 expression later in inf ection might be involved in turning off the inflammatory response and promoting an antigen-specific humoral immune response. Interleukin-4 e fficiently suppressed inflammatory cytokine production in alveolar mac rophages. Its expression was induced in peripheral blood mononuclear c ells by TNF, IL-4, and by reexposure to a specific antigen. To obtain the maximum amount of information on the role of inflammatory cytokine s in animals of veterinary significance it will be useful to perform s tudies in species such that evolutionary relatedness will allow widesp read application of the findings. Furthermore, the variety of molecule s involved in inflammatory cytokine regulation will require much more extensive investigations of the relevant enzymes, inhibitors and recep tors in veterinary species. Finally, the complexity and redundancy of immune defenses in animals mean that attempts to modulate health statu s through manipulation of inflammatory cytokines must be performed wit h caution and that a multiplicity of processes will be affected.