The Effect of Cimetidine and Aminoguanidine on Pro-inflammatory Cytokines in the Horse

In this study, six horses each had three subcutaneous tissue chambers. Each horse was pretreated with intravenous saline (control), cimetidine, or aminoguanidine with a 4-week washout period. On day 0, a carrageenan (NaCl inflamed) was instilled in 1 tissue chamber. Blood and all tissue chamber fluids were sampled on days -1 to 3 and measured for activity levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6. The Tmax for all cytokines (TNF-α, IL-1, IL-6) was 0.5 and 1 day post-inflammation in tissue chamber fluid. In the tissue chamber fluid, NaCl inflamed (NaCl-I), cimetidine, and aminoguanidine groups showed significant increases in IL-1 production. In the NaCl-I and cimetidine, tissue chamber fluid IL-6 was significantly increased when compared with NaCl noninflamed (NaCl-N) for the periods of study -1 to 1, -1 to 2, and -1 to 3. The cimetidine tissue chamber fluid [TCF] appeared to have a delayed, but greater, IL-6 response than the NaCl-I treatment. Even with cimetidine and aminoguanidine pretreatment, the resulting decrease in NO production demonstrated in our previously reported results in these same animals appeared to be too late to decrease the early cytokine response. However, it may assist in preventing the subsequent NO-induced upregulation of pro-inflammatory cytokine production.