Protective effect of pentoxifylline plus thalidomide against septic shock in mice

Mortality caused by septic shock in experimental animals is reduced by thal idomide, an inhibitor of tumour necrosis factor alpha. Another drug that co uld act on the pathopysiological mechanisms of septic shock is pentoxifylIi ne, an inhibitor of platelet aggregation that increases the flexibility of the erythrocyte membrane and has fibrinolytic activity. We studied the effe ct of pentoxifylline alone and combined with thalidomide in septic shock; 9 7 NIH mice were injected with lipopolysaccharides of Salmonella abortus equ i and D galactosamine. Animals were separated in 4 groups; group A (n = 20) was used as control, group B (n = 15) received thalidomide 50 mg/kg, group C (n = 20) received pentoxifylline 40 mg/kg, and group D (n = 15) received thalidomide plus pentoxifylline. Mortality was recorded every hour. Additi onally, 5 animals from each group were sacrificed 8 h after the induction o f septic shock for histological analysis of heart, lung, brain, kidney, sma ll intestine, adrenal glands and liver. Microscopic findings were rated as absent, mild, moderate and severe damage. In control animals histological a nalysis showed intense haemorrhage and necrosis in all organs studied. When compared with controls, treatment with pentoxifylline plus thalidomide red uced mortality (P < 0.03). The tissue damage was less severe in animals fro m the groups that received pentoxifylline or pentoxifylline plus thalidomid e (P < 0.05). Pentoxifylline seems to potentiate the beneficial effects of thalidomide, reducing mortality and attenuating the pathological changes pr oduced by septic shock.