| Abstrakt: |
The incidence of severe invasive disease caused by serogroup A streptococci GAS is increasing, and to elucidate the role of streptococcal cell wall components in the inflammatory response, human whole blood was stimulated with lipoteichoic acid LTA, 0.00550 gmL and peptidoglycan 10 and 100 gml from Streptococcus pyogenes. Both stimulants increased dose dependently the leukocyte release of cytokines many thousand fold tumor necrosis factor alpha 0 to 158,000 ± 4,900 pgmL, interleukin IL1 85 ± 56 to 31,000 ± 4,600 pgmL, IL6 30 ± 11 to 34,800 ± 15,000 pgmL, and IL8 300 ± 150 to 29,000 ± 14,000 pgmL. Intracellular leukocyte levels of reactive oxygen species ROS as measured by flow cytometry increased 1520 fold, from 25 to 400500 mean fluorescence intensity. Aminoethylisothiourea AEITU, a relatively selective inhibitor of the inducible nitric oxide synthase iNOS and a ROS scavenger, reduced the cytokine production by 70100, and intracellular leukocyte ROS levels by 5070 all P< 0.05. The nonselective NOS inhibitor NnitroLarginine methyl ester LNAME did not affect intracellular ROS levels, but it caused a moderate selective inhibition of IL8 production. Leukocyte NO production measured up to 36 h was not enhanced by LTA, peptidoglycan, inactivated streptococci, or cytokine combinations. The mechanisms for the antiinflammatory effects of AEITU may be through a reduction of intracellular ROS levels, or through a direct effect on signal transduction, whereas NO modulation is an unlikely mechanism. |
