1 Oxford Research Forum Journal. Vol. 2, No.1. 17-30, 2004 Assessment of Cytokine Release in Septic Shock Induced by Some Antibiotics Adel Assiri, Hisham A. Awad, Layla E. Borham, and Heba M. Shaker* Pharmacology and Toxicology Department – Faculty of Medicine – Umm Al Qura University Clinical Pathology Department- National Cancer Institute - Cairo University* Abstract Background: To date, the precise pathogenic mechanisms responsible for gram-negative bacterial sepsis have not been fully identified. Although antimicrobials are the primary treatment options for sepsis, they also have the potential to worsen the inflammatory state in some patients. Aim: The aim of the present study is to investigate the pathogenesis of sepsis syndrome in a rat model of Gram- negative sepsis, which are injected by Escherichia coli bacteria with or without antimicrobial therapy, comparing three antimicrobials with different endotoxin-liberating potentials. Methods: Rats were divided into 7 groups. G1: Normal control group, G2: E. coli infected untreated. G3: Infected, cefotaxime (90 mg/kg) treated. G4: Infected, gentamicin (7.2 mg/kg) treated. G5: Infected, clindamycin (27 mg/kg) treated. G6: Infected, cefotaxime and clindamycin treated. G7: Infected, gentamicin and clindamycin treated. Measurements: In all groups, mean arterial blood pressure, heart rate, temperature, and percent lethality were measured, and blood samples were collected at zero time, 3, 6, 12, and 24 hours from antimicrobial injection. White blood cell (WBCs) count, TNF-, IL-6, and erythropoietin plasma levels were measured. Results: Induction of sepsis in rats by intraperitoneal injection of E-coli (G2) produced a statistically significant reduction in mean arterial blood pressure (MBP), and in white blood cell count (WBCs) which showed a marked significant elevation after 12 and 24 hours, a statistically significant elevation in heart rate (HR), rectal temperature, tumor necrosis factor- (TNF-), interlukin-6 (IL-6), and plasma erythropoietin, when compared with control G1. In cefotaxime treated G3, rectal temperature started to be decreased significantly after 12 hours and MBP significantly increased and HR significantly decreased after 6 hours, a significant elevation in TNF-, IL-6 and plasma erythropoietin levels, and a significant reduction in WBCs count when compared with G2. Rats of G4 treated with gentamicin showed a significant elevation in MBP and a significant reduction in HR, TNF-, IL-6, WBCs count and plasma erythropoietin, rectal temperature started to be decreased significantly after 3 hours, when compared with G2. Clindamycin (G5) produced a significant increase in MBP, IL-6, and plasma erythropoietin, and a significant reduction in HR, TNF-, rectal temperature, WBCs count, when compared with G2. Combination of clindamycin with cefotaxime (G6) or