EFFECTS OF L-CARNITINE ON SERUM TRIGLYCERIDE AND CYTOKINE LEVELS IN RAT MODELS OF CACHEXIA AND SEPTIC SHOCK

Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fa tty acid oxidation and muscle protein wasting are common in patients w ith sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxi dation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in ra ts. In the LPS model, rats were injected with LPS (24 mg kg(-1) i.p.), and treated with carnitine (100 mg kg(-1) i.p.) at -16, -8, 0 and 8 h post LPS. Rat health was observed, and plasma inflammatory cytokines and triglycerides (TG) were measured before and 3 h post LPS. In the s arcoma model, rats were implanted subcutaneously with tumour, and trea ted continuously with carnitine (200 mg kg(-1) day(-1) i.p.) via impla nted osmotic pumps. Tumour burden, TG and cytokines were measured week ly for 4 weeks. Carnitine treatment significantly lowered the tumour-i nduced rise in TG (% rise) in the sarcoma model (700 +/- 204 vs 251 +/ - 51, P < 0.03) in control and carnitine groups respectively. Levels o f interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necr osis factor-alpha (TNF-alpha) (pg ml(-1)) were also lowered by carniti ne in both LPS (IL-1 beta: 536 +/- 65 vs 378 +/- 44: IL-6: 271 +/- 29 vs 222 +/- 32; TNF-alpha: 618 +/- 86 vs 367 +/- 54, P less than or equ al to 0.02) and sarcoma models (IL-1 beta: 423 +/- 33 vs 221 +/- 60; I L-6: 222 +/- 18 vs 139 +/- 38; TNF-alpha: 617 +/- 69 vs 280 +/- 77, P less than or equal to 0.05) for control and carnitine groups respectiv ely. We conclude that carnitine has a therapeutic effect on morbidity and lipid metabolism in these disease models, and that these effects c ould be the result of down-regulation of cytokine production and/or in creased clearance of cytokines.