Objective:

Erythropoietin (EPO) was originally identified as a hormone for adjustment of the circulating erythrocyte mass. Following molecular biologic studies today it is known that EPO is a member of the cytokine superfamily with significant homology to mediators of growth and inflammation. In this study, we questioned the antibacterial effect of EPO against an intracellular pathogen.

Methods:

A human isolated, non-mutant, non-37°C resistant Salmonella typhimurium strain was used in experiments. Resting mouse peritoneal macrophages were incubated for 24–48 h with EPO (10 U/mL), EPO/2 (5 U/mL), EPO/4 (2.5 U/mL), l-NAME (nitric oxide inhibitor), EPO/l-NAME, EPO/2/l-NAME in 10:1, 5:1, 1:1 m.o.i. Following incubations extracellular nitric oxide (NO) levels (Griess) were determined; apoptosis (Hoechst 33342)/necrosis (propidium iodide) determinations were made. In simultaneous groups, cells were lysed with sterile distilled water and colony counts were performed.

Results:

Following 24–48 h colony counts were significantly lower in EPO groups compared with EPO/2, EPO/4, Salmonella, l-NAME, EPO/l-NAME groups in 10:1, 5:1, 1:1 m.o.i. Interestingly, NO responses were higher in EPO groups compared with EPO/2, EPO/4, and Salmonella groups. In apoptosis/necrosis balance, apoptosis was dominant in EPO groups compared with EPO/2, EPO/4, Salmonella, EPO/l-NAME, l-NAME groups.

Conclusion:

It is known that EPO is a multifactorial tissue protective cytokine. S. typhimurium shows its pathogenicity by entering the cell, and when enters the cell NO response and apoptosis starts. This study showed that EPO inhibited the entry of S. typhimurium into the macrophages, and simultaneously stimulated NO response which triggered apoptosis more than the bacteria expected.