Abstract

The current proposal will explore the role of cytokines in the response to group B streptococci (GBS) in vitro and in vivo in an experimental model. Studies are designed to examine the sequential appearance of tumor necrosis factor alpha. (TNFa), IL-1 beta (IL-1b), IL-6, and IL-8 following in vitro exposure of human mononuclear cells to GBS. The sequential appearance of these cytokines will also be assessed following GBS inoculation of neonatal rats. We will examine the role of fibronectin (FN) through the critical RGD sequence, in inducing or enhancing TNFa release by human mononuclear cells exposed to group B streptococci. The role of C5a as a co-factor along with GBS in causing cytokine release in vitro will also be explored. These studies will include experiments designed to determine if the GBS C5a-ase can affect C5a induction or enhancement of TNFa release. These studies should yield data that will help to explain the role of the proinflammatory cytokines in the pathogenesis of septic shock due to this most fulminant form of neonatal bacterial infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013150-21
Application #
2886349
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Rubin, Fran A
Project Start
1977-01-01
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2001-08-31
Support Year
21
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Utah
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

La Pine, Timothy R; Joyner, Joanna L; Augustine, Nancy H et al. (2003) Defective production of IL-18 and IL-12 by cord blood mononuclear cells influences the T helper-1 interferon gamma response to group B Streptococci. Pediatr Res 54:276-81
Joyner, J L; Augustine, N H; Taylor, K A et al. (2000) Effects of group B streptococci on cord and adult mononuclear cell interleukin-12 and interferon-gamma mRNA accumulation and protein secretion. J Infect Dis 182:974-7
Kwak, D J; Augustine, N H; Borges, W G et al. (2000) Intracellular and extracellular cytokine production by human mixed mononuclear cells in response to group B streptococci. Infect Immun 68:320-7
Maloney, C G; Thompson, S D; Hill, H R et al. (2000) Induction of cyclooxygenase-2 by human monocytes exposed to group B streptococci. J Leukoc Biol 67:615-21
Takahashi, S; Aoyagi, Y; Adderson, E E et al. (1999) Capsular sialic acid limits C5a production on type III group B streptococci. Infect Immun 67:1866-70
Jaskowski, T D; Martins, T B; Litwin, C M et al. (1999) Comparison of three different methods for measuring classical pathway complement activity. Clin Diagn Lab Immunol 6:137-9
Nester, T A; Wagnon, A H; Reilly, W F et al. (1998) Effects of allogeneic peripheral stem cell transplantation in a patient with job syndrome of hyperimmunoglobulinemia E and recurrent infections. Am J Med 105:162-4
Steele, P M; Augustine, N H; Hill, H R (1998) The effect of lactic acid on mononuclear cell secretion of proinflammatory cytokines in response to group B streptococci. J Infect Dis 177:1418-21
Takahashi, S; Adderson, E E; Nagano, Y et al. (1998) Identification of a highly encapsulated, genetically related group of invasive type III group B streptococci. J Infect Dis 177:1116-9
Bohnsack, J F; Widjaja, K; Ghazizadeh, S et al. (1997) A role for C5 and C5a-ase in the acute neutrophil response to group B streptococcal infections. J Infect Dis 175:847-55

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