Early apoptosis of monocytes contributes to the pathogenesis of systemic inflammatory response and of bacterial translocation in an experimental model of multiple trauma

Summary The objective of this study was to investigate the occurrence of apoptosis ofmonocytes in an experimental model of multiple trauma and its probable cor-relation to bacterial translocation. Thirty-two rabbits were applied in threegroups: A, controls; B, myotomy of the right femur; and C, myotomy and frac-ture of the right femur. Blood was sampled for the estimation of endotoxins[lipopolysaccharide (LPS)], tumour necrosis factor (TNF)- α , malondialde-hyde (MDA) and isolation of peripheral blood mononuclear cells (PBMCs).PBMCs, derived after centrifugation over Ficoll, were incubated in flasks andapoptosis of non-adherent lymphocytes and adherent monocytes was esti-mated after staining for Annexin-V and flow cytometry. TNF- α of superna-tants of cultured monocytes was also determined. Tissue segments werecultured after death. Median survival of groups A, B and C was > 14, > 14 and9·00 days, respectively. Apoptosis of lymphocytes in group C was higher thangroup A at 2, 4 and 48 h and of monocytes in group C higher than group A at2 and 4 hours. LPS in group C was higher than group A at 2, 4 and 48 h. Apo-ptosis of lymphocytes and monocytes was correlated positively with serumTNF-α and negatively with TNF-α of monocyte supernatants. Cultures oforgan segments of group A were sterile. Pseudomonas aeruginosa was isolatedfrom liver, lung and spleen in five animals in group B (45·45%) and in six ingroup C (54·54%). Early apoptosis of blood monocytes supervened after mul-tiple trauma; the phenomenon was accompanied by apoptosis of blood lym-phocytes and subsequent bacterial translocation.Keywords: apoptosis, macrophages/monocytes, stress IntroductionMultiple trauma is a major cause of the systemic inflam-matory response syndrome (SIRS) often accompanied byrapid deterioration of the patient and subsequent death[1]. Current evidence suggests that multiple organ failurein the event of multiple trauma might be connected withthe advent of bacterial translocation and immunoparalysisdue to depletion of lymphocytes [2]. Despite the plethoraof information about lymphocyte apoptosis in multipletrauma, no data are available about monocytes that consti-tute the major determinants of the innate immuneresponse and of the transition of antigenic stimuli to thehost’s adaptive immune system [3]. The present study wasfocused on an experimental model of multiple traumaaiming to define (a) the role of monocyte apoptosis inconjunction to the phenomena of apoptosis of lympho-cytes and of bacterial translocation; and (b) the time-frameof these events.