title: 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.affiliation: Children's Hospital of Orange County, Orange, California 92668, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chang
authors.forename: A
authors.initials: A
authors.lastname: Williams
authors.forename: L
authors.initials: L
authors.lastname: Ishizawa
authors.forename: A
authors.initials: A
authors.lastname: Knoppel
authors.forename: C
authors.initials: C
authors.lastname: van de Ven
authors.forename: M S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D000818:Animals; D015870:Gene Expression; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010976:Platelet Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D013290:Streptococcal Infections / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D013292:Streptococcus agalactiae; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications / Q000517:prevention & control*
chemical_list: D017370:Interleukin-11; D011994:Recombinant Proteins