Investigation of the relation between the hypothalamus-pituitary-adrenal (HPA) axis activity, IL-6 and hyperalgesia during chronic inflammation due to rheumatoid arthritis (RA) in male rats.

Introduction: The activity of Hypothalamus-Pituitary-Adrenal (HPA) axis is increased following inflammation due to its closed relation with immune system. This axis indicates an increased secretion of ACTH, and corticosterone during acute inflammation while little is known about its activity during chronic inflammation such as rheumatoid arthritis (RA). In this study we measured the products of HPA axis and their relation with IL-6 and hyperalgesia during rheumatoid arthritis. Methods: Fourteen Wistar rats were divided in two groups. RA was induced by subcutaneous injection of complete freund’s adjuvant (CFA) to right hind paw of group 1 and the next group was considered as sham control. The levels of ACTH, corticosterone and IL-6 in blood samples were assessed using specific rat ELISA kits on zero, 6th and 21st days. Hyperalgesia was assessed using radiant hit instrument at the same days. Results: The results indicated a significant increase of IL-6 on days 6th and 21st in comparison with day 0. ACTH and corticosterone levels also significantly increased on the 6th day in the RA group in comparison with the control group, but there was no significant increase on the day 21st. Pain threshold was significantly decreased on the 6th day of intervention comparing to the day 0 in the RA group. On the 21st day of intervention, no significant hyperalgesia in the RA group was observed. Conclusion: The activation of HPA axis which is known to respond to IL-6, decreased during RA. ACTH and corticosterone secretion were not modulated during chronic inflammation in this study. On the other hand, long term RA symptoms such as hyperalgesia can be due to the effect of other modulators and independent on HPA axis and immune system.