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

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/mm3, n = 5) compared to that of uninfected neonatal rats (NR) (635.2 +/- 89 K/mm3, 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 micrograms/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/mm3, p < 0.01; 36 hr: 276 +/- 60 vs. 82 +/- 33 K/mm3, p < 0.01; 48 hr: 402 +/- 77 vs. 101 +/- 82 K/mm3, 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 > or = 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 > or = 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.

• Authors: M Chang, A Williams, L Ishizawa, A Knoppel, C van de Ven, M S Cairo
• Journal: Blood cells, molecules & diseases (Blood Cells Mol Dis) Vol. 22 Issue 1 Pg. 57-67 ( 1996) ISSN: 1079-9796 [Print] United States
• PMID: 8807086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-11
• Recombinant Proteins

Topics

• Animals
• Gene Expression
• Interleukin-11 (genetics, metabolism, pharmacology)
• Platelet Count
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (genetics, pharmacology)
• Sepsis (blood, complications, prevention & control)
• Streptococcal Infections (blood, complications, prevention & control)
• Streptococcus agalactiae
• Thrombocytopenia (blood, complications, prevention & control)