Evaluation of Inteiueukin-1 Receptor Antagonist (Il-1ra) and Tumor Necrosis Factor Binding Protein (TNF-BP) in a Rodent Abscess Model of Host Resistance

Abstract

Modulation of pro-inflammatory cytokine responses can alter the normal protective mechanisms against invading pathogens. The cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are crucial in the inflammatory cascade for upregulation of adhesion molecule expression, neutrophil recruitment, and additional cytokine induction. To determine if the cytokine antagonists interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor-binding protein (TNF-bp) alter host resistance mechanisms they were evaluated in a rodent abscess model. It has previously been shown that subcutaneous Staphylococcus aureus injections induce abscess formation in rats. These abscesses can be examined over a pre-determined time course for evaluation of size, severity and time to resolution. Treatment with immunosuppressive drug therapy can modify the normal course of abscess formation and/or resolution. IL-1ra and TNF-bp were administered either alone or in combination. Also, the effects of these cytokine antagonists in combination with dexamethasone were tested. Results indicated TNF-bp at any dose examined did not adversely alter any parameter of abscess formation or resolution. In contrast, high doses of IL-1ra increased abscess severity, while more clinically relevant doses did not. Combination treatment with IL-1ra and TNF-bp did not alter abscess parameters above individual findings. Dexamethasone, given in combination with either cytokine antagonist, significantly increased severity grading scores above dexamethasone given alone. Overall the data indicated high dosing regimens of IL-1ra or TNF-bp only caused transient impacts on this host resistance model, while more clinically relevant doses did not impact any aspect of the abscess. These findings demonstrate that these anti-cytokine therapies do not alter general host resistance.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady

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