Neopterin production and tryptophan degradation in humans infected by Streptococcus pyogenes

Streptococcus pyogenes may cause tonsillitis, scarlet fever and so-called " streptococcal toxic shock-like syndrome" (STSS). These streptococci produce exotoxins which are implicated as superantigens in the pathogenesis of STS S and scarlet fever. Using human peripheral blood-derived mononuclear cells in vitro, such toxins were shown to induce neopterin production and degrad ation of the amino acid tryptophan to metabolites such as kynurenine by act ivating indoleamine (2,3)-dioxygenase via interferon-gamma. We investigated the sera of seven patients with streptococcal tonsillitis and of four pati ents with STSS. Those with STSS showed higher serum neopterin concentration s (median: 152 nmol/l; 95th percentile in healthy controls: 8.7 nmol/l) tha n those with tonsillitis (median: 12 nmol/l). Similarly, kynurenine to tryp tophan ratios were increased in tonsillitis and extremely high in patients with STSS. Highly increased neopterin production and tryptophan degradation in patients with STSS suggest an association between a high degree of T ce ll activation and the severity of the disease manifestation.