Streptococcal pyrogenic exotoxin A (SPE A) superantigen induced production of hematopoietic cytokines, IL-12 and IL-13 by human peripheral blood mononuclear cells.
A quantitative and kinetic study of the release of the hematopoietic cytokines IL-3, IL-5 and GM-CSF, the immunoregulatory cytokine IL-12 heterodimer (and its p40 subunit) and IL-13 by human peripheral blood mononuclear cells (PBMC) stimulated in vitro with the superantigen streptococcal pyrogenic (erythrogenic) exotoxin A (SPE A) from Streptococcus pyogenes is reported. PBMC were stimulated in parallel with heat-killed group A streptococcal cells, E. coli lipopolysaccharide (LPS) and with concanavalin A (Con A) in certain experiments for comparative purposes. The cytokines were assayed in the supernatant fluids by ELISA. IL-13 expression was also determined by a quantitative competitive PCR. IL-3, IL-5, GM-CSF, IL-12 p40, IL-12 heterodimer and IL-13 expression was induced by SPE A in a time- and dose-dependent manner in rather substantial amounts except the IL-12 heterodimer, which was released in small quantities. In contrast to SPE A, IL-3, IL-5 and IL-13 were not or poorly elicited by streptococcal cells or LPS whereas these two stimulants induced relatively high amounts of GM-CSF. Interestingly, both IL-12 p40 and IL-12 heterodimer were released in much higher amounts by streptococcal cells. Con A induced IL-3, IL-5, GM-CSF and IL-13 production in amounts comparable to those elicited by SPE A. The possible pathophysiological relevance of the elicitation by SPE A and streptococcal cells of these cytokines is discussed.
Müller-Alouf
H
H
Unité INSERM 167, Institut Pasteur, Lille, France.
Gerlach
D
D
Desreumaux
P
P
Leportier
C
C
Alouf
J E
JE
Capron
M
M
D001426:Bacterial Proteins; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D019281:Dimerization; D004926:Escherichia coli; D005098:Exotoxins / Q000633:toxicity*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000097:blood; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000097:blood; D007377:Interleukin-3 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008565:Membrane Proteins; D016133:Polymerase Chain Reaction; D013297:Streptococcus pyogenes; D018089:Superantigens / Q000633:toxicity*
D001426:Bacterial Proteins; D016207:Cytokines; D005098:Exotoxins; D018793:Interleukin-13; D007377:Interleukin-3; D015848:Interleukin-5; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C027951:erythrogenic toxin; D003208:Concanavalin A; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor