Endogenous Interleukin-11 (IL-11) Expression Is Increased and Prophylactic Use of Exogenous IL-11 Enhances Platelet Recovery and Improves Survival During Thrombocytopenia Associated With Experimental Group B Streptococcal Sepsis in Neonatal Rats

Abstract

ABSTRACT Future preventive and/or concurrent therapy of neonatal sepsis may require the use of adjuvant immunohematopoietic therapy. In the present study, using reverse transcription-polymerase chain reaction, we demonstrated a significant increase in IL-11 mRNA extracted from the femurs of group B streptococcus (GBS)-infected rats during acute thrombocytopenia (platelet count: 65.8 ± 19.3 K/mm 3, n=5) compared to that of uninfected neonatal rats (NR) (635.2 ± 89 K/mm 3, n=5) (174 ± 17% vs. 100%, p<0.001, n=5). We next investigated the prophylactic effect of rhIL-11 on the PLT recovery as well as survival in NR during experimental GBS sepsis. NR received either rhIL-11 (250 μg/kg/d) intraperitoneally for 11 d or sham injections before the induction of experimental GBS sepsis. While experimental GBS sepsis resulted in severe thrombocytopenia in control NR, the rhIL-11 pre-treated group had significantly higher PLT counts (24 hr: 417 ± 50 vs. 221 ± 54 K/mm 3, p<0.01; 36 hr: 276 ± 60 vs. 82 ± 33 K/mm 3, p<0.01; 48 hr: 402 ± 77 vs. 101 ± 82 K/mm 3, p<0.05). Administration of rhIL-11 alone also significantly increased the survival rate at 36 and 48 hrs after GBS inoculation compared to the control group (36 hr: 83% vs. 58%, p<0.05; 48 hr: 50% vs. 18%, p<0.01, n≥30), as did the combination of rhIL-11 with ABS treatment at 36 hrs, compared to the control group (90% vs. 69%, p<0.05, n≥30). These results suggest that endogenous IL-11 gene expression may be upregulated during acute thrombocytopenia and associated bacterial sepsis in NR. This increase in IL-11 gene expression, however, does not appear to prevent severe thrombocytopenia. Furthermore, prophylactic administration of pharmacological doses of rhIL-11 may be potentially beneficial in the management of neonatal GBS sepsis and its associated thrombocytopenia. Future studies are needed to determine the clinical implications of these findings.