Based on clinical data revealing a promising immunomodulatory effect of
clarithromycin in
sepsis due to
ventilator-associated pneumonia, the efficacy of
clarithromycin in experimental
peritonitis and
sepsis was assessed with particular emphasis on immune function. Cecal
puncture and
ligation was performed in rabbits assigned to the following groups: Group A, controls (n=12); Group B, intravenous
clarithromycin treatment (n=15); Group C,
piperacillin/tazobactam (TZP) treatment (n=10); Group D, clarithromycin+TZP combination treatment (n=12). Blood was sampled at serial time intervals and peripheral blood mononuclear cells (PBMCs) were isolated. Apoptosis of lymphocytes and monocytes was measured by flow cytometric analysis. PBMCs were stimulated with
lipopolysaccharide (LPS) and
Pam3Cys for the release of tumour
necrosis factor-alpha (TNFα). Tissue bacterial growth was quantitatively measured after death or sacrifice. Survival in Group D after 10 days was prolonged compared with the other groups. Early apoptosis of lymphocytes in Group B was lower compared with Group
D at 2h and compared with Group C at 4h. Early apoptosis of monocytes in Group B was lower compared with Group C at 24h. Following stimulation of PBMCs with LPS, release of TNFα was decreased in Group B compared with Groups A and
D at 2h. Bacterial growth in tissues of Groups C and D was decreased compared with Group A. It is concluded that
clarithromycin modulates the function of the immune response in experimental
peritonitis by decreasing the rate of early apoptosis of lymphocytes and monocytes and by decreasing the ex vivo release of TNFα by blood monocytes.