Dual effect of melatonin as proinflammatory and antioxidant in collagen‐induced arthritis in rats

Abstract

The aim of this study was to determine the effects of melatonin on proinflammatory status of rats with collagen-induced arthritis (CIA). CIA was induced in male Wistar rats with an emulsion of type II collagen in Freund's Incomplete Adjuvant (C-II/FIA). For 14 days, control and pinealectomized rats received a subcutaneous injection of 100 microL melatonin (30 microg) or vehicle (saline on 1% ethanol). Levels of cytokines interleukin (IL)-1beta and IL-6 were determined in the serum, peripheral blood mononuclear cells, and joints. Levels of anti-type II collagen antibody, nitrite/nitrate, and lipid peroxidation (LPO) were determined in the serum, joints, and brain. Treatment with melatonin significantly increased the levels of IL-1beta, IL-6, nitrite/nitrate and LPO in joints. However, melatonin significantly reduced the levels of nitrite/nitrate and LPO in serum and brain. Moreover, CIA in pinealectomized rats presented significantly reduced levels of IL-1beta and IL-6, titers of anti-type II collagen antibodies, levels of nitrite/nitrate, and LPO in joints but elevated levels in serum and brain. Melatonin has been described as a proinflammatory and antioxidant agent. In a process of inflammation as CIA, melatonin acts with a markedly proinflammatory effect at local and peripheral levels maintaining its antioxidant effect only at peripheral level.

Modulation of C-reactive protein and tumour necrosis factor-alpha in collagen-induced arthritis in Dark Agouti rats: impact of collagen concentration on severity of arthritis

“…Increase in concentration of collagen in suspension had a more significant effect on the severity of arthritis indicated by significant elevation in TNF-a levels as observed in the 4 mg/kg body weight group. TNF-a contributes to the cellular damage in arthritis [14,18]. High levels of this cytokine in circulation indicate the progression of cartilage cell injury in arthritis.…”

Sex-Dependent Effect of Melatonin on Systemic Erythematosus Lupus Developed in Mrl/Mpj-Faslpr Mice: It Ameliorates the Disease Course in Females, whereas It Exacerbates It in Males

“…Thus, MRL/MP-fas lpr mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase (3). On the contrary, melatonin can also regulate the immune system (4) and can play a role in autoimmune diseases such as rheumatoid arthritis (5,6) and Crohn's disease (7).…”

Multiple Facets of Melatonin in Immunity: Clinical Applications

“…An additional study showed a dual effect of melatonin, which increased serum anticollagen antibodies titers together with IL-1β and IL-6 levels in serum and joints of arthritic rats, while it decreased oxidative markers in serum but not in joints. As expected, pinealectomy effects were opposed, with a reduction in antibodies, cytokine levels, and oxidative stress in joints, but elevated oxidative markers in serum [ 160 ]. In contrast to those studies supporting the deleterious effect of melatonin, a prophylactic and/or therapeutic treatment with the indoleamine reduces hind paw swelling in a similar way as indomethacin does in an adjuvant-induced arthritis model [ 161 ].…”