REPLY: Leptospirosis is a zoonotic disease of global importance and can be caused by any one of more than 11 species and 200 serovars of spirochetes of the genus Leptospira (2). In recent years, a severe form of leptospirosis, involving pulmonary hemorrhage, has emerged as a serious clinical syndrome (8, 9). The mechanisms of pathogenesis, host defense, and protective immunity remain poorly understood. Understanding the mechanisms of immunity to leptospirosis is of major importance in developing a successful vaccine against leptospirosis as well as in gaining insight into the pathogenesis of natural or induced infection. In an article recently published in AJP-Renal Physiology, we investigated epithelial sodium transporter protein expression in an animal model of leptospirosis with the objective of determining the mechanisms involved in the pathogenesis of pulmonary edema in this condition (1). We found that, in pulmonary cells, expression of epithelial sodium channel protein was reduced, and NKCC1 protein expression was increased. In his Letter to the Editor regarding that same article, Eisenhut (6) hypothesized that the most likely mechanism explaining these changes in epithelial membrane ion transporter protein expression is the effect of the cytokines tumor necrosis factor (TNF) and interleukin (IL)-1. This is a plausible explanation, given that Eisenhut et al. (4, 5) have shown that, in other models of infectious disease, including meningococcemia, such a mechanism is involved. The authors showed that, in meningococcal septicemia patients with pulmonary edema, levels of TNF and IL-1 are high, and systemic epithelial ion transport is impaired, leading to greater fractional excretion of sodium, as well as to elevated levels of sodium in sweat and saliva. In a kinetic study, Vernel-Pauillac and Merien (10) compared the mRNA expression levels of various cytokines in the peripheral blood mononuclear cells of Leptospira interrogansinoculated hamsters. The authors observed pronounced mRNA expression of the Th1 cytokines TNF, interferon(IFN), and IL-12, with transcripts being detected as early as 1 h postinfection. In addition, the expression of anti-inflammatory cytokines, such as IL-4 and IL-10, was prominent from 1 to 4 days postinfection in response to infection with L. interrogans. It has also been demonstrated that levels of soluble IL-2R, IL-6, TNF, IFN, and IL-12 are elevated in sera obtained from patients treated for acute leptospirosis (3, 7). Eisenhut (6) has raised a very interesting point that merits further consideration and investigation.