Relationship among nitric oxide, leptin, ACTH, corticosterone, and IL-1beta, in the early and late phases of adjuvant arthritis in male Long Evans rats.
Leptin, a hormone regulating body weight, food intake, and metabolism, is associated with activation of immune cells and inflammation. In this study we analyzed levels of leptin, adrenocorticotropic hormone (ACTH), corticosterone, interleukin 1beta (IL-1beta), and nitric oxide (NO) production on days 10 and 22 of adjuvant arthritis (AA) in male Long Evans rats to ascertain possible relationship of leptin with its modulators during the early and late phases of chronic inflammation. The circulating leptin levels were significantly reduced already on day 10 of AA compared to controls (1.97+/-0.22 ng/ml vs. 3.08+/-0.25 ng/ml, p<0.05); on day 22 no significant further drop was observed (1.06+/-0.21 ng/ml). Leptin mRNA in epididymal fat tissue was reduced in arthritic animals compared to controls on day 22 (0.61+/-0.09 vs. 1.30+/-0.1 arbU/GAPDH (p<0.01). IL-1beta concentration in spleen was enhanced on day 10 of AA (24.55+/-4.67 pg/100 microg protein vs. 14.33+/-1.71 pg/100 microg protein; p<0.05); on day 22 it did not differ from controls. ACTH and corticosterone levels were significantly elevated only on day 22 of AA (ACTH: 306.17+/-42.22 pg/ml vs. 157.61+/-23.94 pg/ml; p<0.05; corticosterone: 5.24+/-1.38 microg/100 ml vs. 1.05+/-0.23 microg/100 ml; p<0.01). Nitrate levels were enhanced similarly on days 10 (49.86+/-1.83 microM) and 22 of AA (43.58+/-2.17 microM), compared to controls (23.42+/-1.39 microM, p<0.001). These results show that corticosterone does not stimulate leptin production during AA. The suppression of leptin may be a consequence of permanent activation of NO, IL-1beta, and of lower weight gain. Circulating leptin does not seem to play a key role in the progression of chronic arthritis.
Stofkova
Andrea
A
Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine of Charles University, Prague, Czech Republic.
Skurlova
Martina
M
Tybitanclova
Katarina
K
Veselsky
Leopold
L
Zelezna
Blanka
B
Jurcovicova
Jana
J
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D053583:Interleukin-1beta / Q000097:blood*; D020738:Leptin / Q000097:blood* / Q000235:genetics; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D053583:Interleukin-1beta; D020738:Leptin; D012333:RNA, Messenger; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone