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

Future preventive and/or concurrent therapy of neonatal sepsis may req uire the use of adjuvant immunohematopoietic therapy. In the present s tudy, using reverse transcription-polymerase chain reaction, we demons trated a significant increase in IL-11 mRNA extracted from the femurs of group B streptococcus (GBS)-infected rats during acute thrombocytop enia (platelet count: 65.8 - 19.3 K/mm(3), n=5) compared to that of un infected neonatal rats (NR) (635.2 - 89 K/mm(3), n=5) (174 - 17% vs. 1 00%, p<0.001, n=5). We next investigated the prophylactic effect of rh IL-11 on the PLT recovery as well as survival in NR during experimenta l GBS sepsis. NR received either rhIL-11 (250 g/kg/d) intraperitoneall y for 11 d or sham injections before the induction of experimental GBS sepsis. While experimental GBS sepsis resulted in severe thrombocytop enia in control NR, the rhIL-11 pre-treated group had significantly hi gher 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/m m(3), p<0.05). Administration of rhIL-11 alone also significantly incr eased the survival rate at 36 and 48 hrs after GBS inoculation compare d to the control group (36 hr: 83% vs. 58%, p<0.05; 48 hr: 50% vs. 18% , p<0.01, n greater than or equal to 30), as did the combination of rh IL-11 with ABS treatment at 36 hrs, compared to the control group (90% vs. 69%, p<0.05, n greater than or equal to 30). These results sugges t that endogenous IL-11 gene expression may be upregulated during acut e thrombocytopenia and associated bacterial sepsis in NR. This increas e in IL-11 gene expression, however, does not appear to prevent severe thrombocytopenia. Furthermore, prophylactic administration of pharmac ological doses of rhIL-11 may be potentially beneficial in the managem ent of neonatal GBS sepsis and its associated thrombocytopenia. Future studies are needed to determine the clinical implications of these fi ndings.