Pro-inflammatory cytokines in a ruminant model: pathophysiological, pharmacological, and therapeutic aspects

Infection evokes complex changes which are thought to be caused by production and release of pro-inflammatory cytokines such as tumour necrosis factor (TNF-alpha), interferons (INFs), and interleukins (ILs). They regulate local inflammatory reactions, but may also gain access to the circulation and induce systemic effects collectively known as the Acute Phase Response. To improve our understanding of the pathophysiology of pro-inflammatory cytokines in ruminants, studies have been performed with TNF-alpha, IL1-alpha/beta, and IFN-alpha/ gamma as well as with cytokine-inducers in dwarf goats. In relation to therapy, the following aspects may be of interest: a) Cytokine therapy given before or just after microbial challenge induces in vivo antimicrobial activity. Moreover, cytokines potentiate in vivo the antimicrobial activity of antibiotics, b) Cytokines may act as biological response modifiers for enhancing specific immunity to vaccines, and c) Cytokines may affect drug absorption, disposition, and metabolite formation in disease states. Although studies of the actions of corticosteroids, nonsteroidal anti-inflammatory and antipyretic agents, antibodies to endotoxin, TNF-alpha, or IL-1, synthetic E. coli lipid A precursors, hydrazine, isoniazid, chloroquine, polymyxin B, bicyclic imidazoles, hydroxamates, and tyrosine kinase inhibitors in endotoxaemic animals have shed further light on inflammatory processes, clinical studies in this field are urgently required to evaluate their beneficial effect.