Synergism between IL-1 beta and TNF-alpha on the activity of the pituitary-adrenal axis and on food intake of rats

Abstract

Experimental procedures. To diminish the stress by the experimental procedures, the animals were handled daily by the experimentator, starting 1 wk before cannulation. Blood was collected from freely moving rats by means of a chronic cannula. Rats were cannulated according to the method described by Steffens (26), with some minor modifications, as described earlier (29). Briefly, under Hypnorm (0.5 ml/kg body wt im; 10 mg/ml fluanisone and 0.315 mg/ml phentanyl citrate; Janssen Pharmaceutica, Tilburg, The Netherlands)-Dormicum (1.0 ml/kg body wt ip; 5.0 mg/ml midazolam hydrochloride; Hoffmann-La Roche, Mijdrecht, The Netherlands)-atropine (0.025 mg/rat sc; Pharmachemie, Haarlem, The Netherlands) anesthesia, a Silastic cannula (ID 0.5 mm; OD 0.94 mm; Dow Corning, Midland, MI) was inserted into the right external jugular vein and passed down to the atrium. The distal end of the cannula was tunneled subcutaneously and exteriorized through a stab wound on the skin of the head, where it was connected to a hooked stainless steel tube. This assembly was anchored to the skull with three stainless steel screws and acrylic cement. During cannulation, rats were continuously exposed to a gas flow of O2-N2O (each 500 ml/min). To keep the cannula patent, it was filled with a 0.9% NaCl solution containing heparin (500 IU/ml; Organon Teknika, Boxtel, The Netherlands) and polyvinylpyrrolidone (1 g/ml; Merck, Darmstadt, Germany).Seven or eight days after cannulation, rats were equipped with intraperitoneally implanted osmotic minipumps (1 (xl/h for 3 days, model 1003D; Alzet, Palo Alto, CA), which were loaded with either sterile pyrogen-free physiological saline or saline containing IL-1, TNF, or IL-1 in combination with TNF. After loading, the pumps were equilibrated and immersed in saline at 37°C for 3-4 h according to the instructions of the manufacturer. The pumps were implanted intraperitoneally under halothane (ICI Pharmaceuticals, Macclesfield, UKJ-CV N20 anesthesia between 1430 and 1630. The indwelling cannula and the osmotic minipumps were tolerated well by the animals, with no signs of discomfort or infection.Protocol. A total of eight groups of rats was continuously infused with saline, IL-1, TNF, or with a combination of IL-1 and TNF. One group of rats was infused with 2.0 (xg IL-1/day

Synergistic Effects of Interleukin-1β, Interleukin-6, and Tumor Necrosis Factor-α Central Monoamine, Corticosterone, and Behavioral Variations

“…With respect to consumption of a favored food substance, it appeared that IL-6 did not enhance the effects of either IL-1␤ or TNF-␣. In contrast, the co-administration of behaviorally sub-effective doses of IL-1␤ and TNF-␣ appeared to synergistically influence consumption, as previously observed with respect to feeding patterns Van der Meer et al 1995;Yang et al 1994).…”

Cytokines, “Depression Due to A General Medical Condition,” and Antidepressant Drugs

“…Exogenous administration of TNFa produced anorexia, body weight loss, and pituitary-adrenal activation (Plata-Salaman, 1998;Sonti et al, 1996;Van der Meer, Fred Sweep, Pesman, Borm, & Hermus, 1995;Warren, Finck, Arkins, Kelley, Scamurra, Murtaugh, & Johnson, 1997). Moreover, TNFa synthesis blockers or antibodies to TNFa suppressed the anorexia, body weight loss, and adrenocortical activation produced by various immune chaflenges (Breuille, Farge, Rose,Arnel,Attaix, & Obled, 1993;Smith, & Kluger, 1993;Wohlman, Gallily, Yirmiya, & Weidenfeld, 1997).…”

Toll-like receptor 4 plays a crucial role in the immune–adrenal response to systemic inflammatory response syndrome

“…After treatment with cLPS, the lack of response to adrenal corticosterone could also have been caused by the abolished activation of IL-1␤, TNF-␣, and IL-6. These cytokines are released by peripheral immune cells in response to an endotoxin challenge, and through the activation of the HPA axis, they regulate corticosterone secretion (36,37).…”