The sepsis syndrome is associated with the presence of circulating proinflammatory cytokines. Recent investigations have indicated the presence of naturally occurring antiinflammatory mediators (such as interleukin-1ra, soluble tumor necrosis factor receptor [sTNF R], and interleukin-10). Among the anti-inflammatory cytokines, transforming growth factor-ß 1 (TGF-ß 1) has been shown to repress the production of inflammatory cytokines by activated macrophages [1] and to induce the release of sTNF R and interleukin-1ra [2]. Circulating TGF-ß 1 levels are present in healthy persons, and the role of TGF-ß 1 in homeostasis has been clearly established in knock-out mice, which die within 3 weeks of developing multifocal inflammatory disease [3].

We investigated whether the levels of circulating TGF-ß 1 were increased in patients with the sepsis syndrome. We measured the levels of plasma TGF-ß 1 in 26 patients at the time of diagnosis. As shown in Table 1, mean plasma levels of TGF-ß 1 were significantly higher in septic patients than in healthy donors. In 8 patients, the circulating TGF-ß 1 level was greater than 26.6 ng/mL, which was the highest level observed in the healthy donors. When levels in platelet-poor plasma were measured, the difference between the groups was borderline. Levels of TGF-ß 1 were not correlated with outcome or other cytokine levels. These results indicate that high levels of circulating TGF-ß 1 can be associated with the sepsis syndrome. The contribution of platelets as a source of this cytokine in plasma may be increased during sepsis. The immunosuppression seen in experimental sepsis and in patients with the sepsis syndrome might reflect the presence of increased levels of TGF ß 1 [4].

In conclusion, it appears that what Louis Pasteur called "Natura medicatrix" when he studied puerperal sepsis [5] occurs in many patients with the sepsis syndrome. In other words, the systemic inflammatory response syndrome is associated not only with the exacerbation of the production of proinflammatory cytokines but also with the increased release of many anti-inflammatory actors, including specific interleukin-1 and tumor necrosis factor inhibitors and such cytokines as interleukin-10 and TGF-ß 1.