The pyrogenic effect of scarlet fever toxin

Scarlet fever toxin was found to liberate leukocytic pyrogen from granulocytesin vitro. In comparative experiments withSalmonella paratyphi B endotoxin and scarlet fever toxin it was tested whether leukocytes from rabbits tolerant to one of these toxins are able to synthetize and liberate endogenous pyrogen. Leukocytes from rabbits tolerant to endotoxin liberated leukoeytic pyrogen following challenge with endotoxin or with scarlet fever toxin. Leukocytes from animals tolerant to scarlet fever toxin liberated leukocytic pyrogen in the presence of endotoxin, but were insensitive to homologous, i.e. scarlet fever toxin. Similarly, leukocytes from cortisone-treated animals did not liberate leukocytic pyrogen if they were incubated with scarlet fever toxin, but liberation of leukocytic pyrogen did take place under challenge with endotoxin. Leukocytes from normal animals incubated in Hanks solution without toxin did not synthetize endogenous pyrogen.     

The pyrogenic effect of scarlet fever toxin

The scarlet fever toxin is pyrogenically active. The pyretic reaction can be inhibited with antiserum bothin vitro andin vivo. From the quantitative aspect the pyrogenicity neutralization point corresponds approximately to the equivalence point of the flocculation reaction. The transmission of tolerance with the serum of tolerant animals failed. Tolerance was of short duration; interruption of the series of toxin injections for two days resulted in complete restoration of the animal's sensitivity. It is argued on the basis of these results that although tolerance carries signs of immunological specificity it cannot be explained in terms of circulating antibodies.     

The pathophysiological effect of scarlet fever toxin

The intravenous injection of scarlet fever toxin leads to acute changes in the white blood picture. The changes are correlated to the dose; a small dose causes lymphopenia and granulocytosis, while higher doses are followed by initial granulocytopenia. Tolerant rabbits do not have granulocytopenia, but lymphopenia persists. Tolerance to the leucopenic effect of the toxin probably develops somewhat sooner and lasts longer than tolerance to its pyrogenic effect. The blood picture of a cortisone-treated rabbit after the intravenous injection of scarlet fever toxin resembles the blood picture of a tolerant rabbit. The significance and associations of these observations are briefly discussed.     

The pyrogenic effect of scarlet fever toxin

Glucocorticoids—hydrocortisone rather more effectively than cortisone—markedly inhibited the pyrogenic and lethal activity of scarlet fever toxin after only two days’ preadministration. Prolongation of preadministration of the steroid to seven days enhanced its protective effect, but the difference was not statistically significant. The systemic administration of glucocorticoids weakened or completely inhibited the development of a positive Dick test, only two days’ preadministration of cortisone being needed for inhibition. The findings are discussed with reference to the question of the nature of the action of scarlet fever toxin in the organism.     

Effect of scarlet fever toxin on the phagocytic activity of the reticuloendothelial system

In normal rabbits and mice, one i.v. injection of scarlet fever toxin (ET) (30 000 STD per kg of rabbit weight or 20-g mouse) elicited a similar biphasic change in carbon clearance rate - early depression followed by a stimulating phase - as has been described for Gram-negative endotoxins. Prolonged depression without a subsequent stimulation phase was obtained in mice by raising the ET dose. The reasons of the discrepancy between these findings and those of Hanna and Watson (1965b) are discussed. Pyrogenic tolerance to ET is not accompanied by accelerated carbon clearance and is not impaired by RES blockade. A possible mechanism of ET tolerance is suggested.     

Influence of antilymphocyte and antipolymorphonuclear sera on the pyrogenic effect of scarlet fever toxin

The role played by lymphocytes in the pyretic response to scarlet fever toxin (ET) was studied in vivo using antilymphocyte serum (ALS). Two i.v. injections of ALS inhibited the pyretic response to a subsequent ET injection in rabbits. The course of endotoxin fever remained uninfluenced by ALS. Antipolymorphonuclear serum had no effect on the pyretic response to either of the toxins. Pretreatment with ALS also inhibited the skin reaction after i.d. injection of ET. These findings are further evidence a mediating role of lymphocytes in the biological effects of ET, among other things in the release of endogenous pyrogen.     

Streptococcal pyrogenic exotoxin type A (scarlet fever toxin) is related to Staphylococcus aureus enterotoxin B

Summary The nucleotide sequence of the gene encoding group A streptococcal pyrogenic exotoxin type A (SPE A) was determined by the dideoxy chain termination method. The first 30 residues of the translation product represented a hydrophobic signal peptide. The mature protein was 220 amino acids in length and had a molecular weight of 25,805. It has significant protein sequence homology with Staphylococcus aureus enterotoxin B but not with other proteins in the Dayhoff library.     

Streptococcal superantigens and the return of scarlet fever

Streptococcus pyogenes (group A Streptococcus) is a globally disseminated and human-adapted bacterial pathogen that causes a wide range of infections, including scarlet fever. Scarlet fever is a toxin-mediated disease characterized by the formation of an erythematous, sandpaper-like rash that typically occurs in children aged 5 to 15. This infectious disease is caused by toxins called superantigens, a family of highly potent immunomodulators. Although scarlet fever had largely declined in both prevalence and severity since the late 19th century, outbreaks have now reemerged in multiple geographical regions over the past decade. Here, we review recent findings that address the role of superantigens in promoting a fitness advantage for S. pyogenes within human populations and discuss how superantigens may be suitable targets for vaccination strategies.     

Epidemiological pattern of scarlet fever in recent years

During the period of 1953-2001 scarlet fever morbidity level fluctuated from 670.3 to 65.9 per 100,000 of the population in Moscow and from 531.9 to 35.0 per 100,000 of the population of the Russian Federation. In recent years an increased morbidity was more pronounced in Moscow than in the Russian Federation as a whole. Children formed the greater part of scarlet fever patients, the cases of scarlet fever among children in Moscow occurring more often than, on the average, in Russia. As before, annual morbidity among children attending children's institutions was higher 3- to 4-fold than among children brought up at home. This difference was most sharply pronounced among young children during the first two years of their life. In contrast to morbidity observed during previous 20-30 years, a drop in morbidity among children during the first two years of their life was registered, while morbidity level among children aged 3-6 years and 7-14 years increased. Scarlet fever morbidity had a pronounced seasonal (autumn-winter) pattern. In a group of children aged 3-5 years who attended organized groups, on the average, 78.6% of scarlet fever cases fell on seasonal morbidity, the most prolonged one.