PCS and IS stimulate significant cellular inflammation. Similar immune and cellular inflammatory responses were induced by PCS or IS on cultured proximal renal tubular cells.

Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that Leptospira santorosai serovar Shermani detergent extract stimulates ECM accumulation in vitro. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The addition of serovar Shermani detergent extract led to an increase in fibronectin gene expression and production. Inhibition of TLR2 but not TLR4 expression abrogated serovar Shermani detergent extract-mediated increases in fibronectin production. This response was also blocked by the knockdown of the gene expression of the TLR2 downstream transducers myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear factor-B, and its inhibition by curcumin-attenuated serovar Shermani detergent extract induced increases in fibronectin production. These effects were also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration of live leptospires to cells also induced fibronectin production that was blocked by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani detergent extract can induce fibronectin production through the TLR2-associated cascade, providing evidence of an association between TLRs and leptospirosis-mediated ECM deposition.

Background: Despite advances in imaging, as well as antibiotic and surgical treatment, spinal epidural abscess (SEA) remains a challenging problem in end-stage renal disease (ESRD) patients. This investigation assesses the influence of ESRD on clinical manifestations, complications, and outcomes in patients with SEA. Methods: This study retrospectively reviewed medical records of 41 patients with SEA treated during [2003][2004][2005][2006]. The patients comprised two groups: group I (patients with ESRD) and group II (patients without ESRD). Patient characteristics, including age, gender, comorbidities, clinical presentations, laboratory data, locations of epidural abscess, and outcome, were recorded and compared. Results: The final sample comprised 41 patients. The mean age of the subjects was 62 + 12 years. The sample included 12 patients with ESRD and 29 without ESRD. The development of symptoms was similar for both groups. Group I patients displayed higher serum erythrocyte sedimentation rate (ESR) (108 + 26 vs. 81 + 31 mm/h, p = 0.014) and lower serum hematocrit (27.1 + 4.3 vs. 33.7 + 5.1%, p < 0.001) than group II patients. Overall survival at 3 months was 88.9% and 93.1% for patients in groups I and II, respectively (p = 0.876). Meanwhile, patients that underwent surgical decompression of epidural abscess received more surgeries than group I patients (1.08 vs. 0.55, p = 0.086), although the difference was not significant. Conclusions: ESRD is a risk factor for repeat surgery in patients with SEA. This investigation suggests that ESRD patients with SEA may require aggressive surgical intervention despite ESRD not affecting their long-term prognosis.