Two murine models of sepsis: immunopathological differences between the sexes-possible role of TGFß1 in female resistance to endotoxemia.

Endotoxic shock (ExSh) and cecal ligature and puncture (CLP) are models that induce sepsis. In this work, we investigated early immunologic and histopathologic changes induced by ExSh or CLP models in female and male mice. Remarkable results showed that females supported twice the LD100 of LPS for males, CLP survival and CFU counts were similar between genders, high circulating LPS levels in ExSh mice and low levels of IgM anti-LPS in males. In the serum of ExSh males, TNF and IL-6 increased in the first 6 h, in CLP males at 12 h. In the liver of ExSh mice, TNF increased at 1.5 and 12 h, IL-1 at 6 h. TGFß1 increased in females throughout the study and at 12 h in males. In CLP mice, IL-6 decreased at 12 h, TGFß1 increased at 6-12 h in males and at 12 h in females. In the lungs of ExSh males, IL-1ß increased at 1.5-6 h and TGFß1 at 12 h; in females, TNF decrease at 6 h and TGFß1 increased from 6 h; in CLP females, TNF and IL-1ß decreased at 12 h and 1.5 h, respectively, and TGFß1 increased from 6 h; in males, TGFß1 increased at 12 h. In the livers of ExSh mice, signs of inflammation were more common in males; in the CLP groups, inflammation was similar but less pronounced. ExSh females had leucocytes with TGFß1. The lungs of ExSh males showed patches of hyaline membranes and some areas of inflammatory cells, similar but fewer and smaller lesions were seen in male mice with CLP. In ExSh females, injuries were less extent than in males, similar pulmonary lesions were seen in female mice with CLP. ExSh males had lower levels of TGFß1 than females, and even lower levels were seen in CLP males. We conclude that the ExSh was the most lethal model in males, associated with high levels of free LPS, low IgM anti-LPS, exacerbated inflammation and target organ injury, while females showed early TGFß1 production in the lungs and less tissue damage. We didn't see any differences between CLP mice.

Association of Nail Dystrophy With Accrued Damage and Capillaroscopic Abnormalities in Systemic Lupus Erythematosus.

BACKGROUND: There are some nail abnormalities described in systemic lupus erythematosus (SLE). OBJECTIVES: The aim of this study was to evaluate the association between nail dystrophy (ND) and disease activity, accrued organ damage, capillaroscopic abnormalities, autoantibodies, and some markers of endothelial cell activation in patients with SLE. METHODS: This was a cross-sectional study of SLE patients from a rheumatology clinic in a tertiary care hospital. Patients were allocated in groups, according to the presence or absence of ND. Demographics, clinical data, disease activity, accrued damage, serology, nailfold capillaroscopy characteristics, serum levels of anti-endothelial cell antibodies, and plasma levels of endothelin 1 were compared between groups. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 index and accrued organ damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. RESULTS: Sixty-one patients were included; 50 patients (82%) were female. Thirty-two patients (52.5%) showed ND, and 29 did not. Besides a more frequent use of cyclophosphamide (46.9% vs 20.7%; P = 0.03) in the ND group, clinical features were similar. A greater organ damage was found in patients with ND (median Systemic Lupus International Collaborating Clinics/American College of Rheumatology index = 0.5, minimum = 0, maximum = 6) than in patients without ND (0, 0, 3, respectively; P = 0.04); specifically, only the skin domain was associated with ND (P = 0.04). Onycholysis (40.6%) and longitudinal ridging (25%) were the most frequent nail changes. Nailfold capillaroscopy changes were more frequent in ND patients (40.6%) than in control subjects (13.8%) (P = 0.02). The most frequent nailfold capillaroscopy findings in the ND group were enlarged capillaries (40.6%) and microhemorrhages (12.5%). There was no association between ND and the autoantibody profile, plasma endothelin 1, or serum anti-endothelial cell antibodies. CONCLUSIONS: Nail dystrophy was associated with higher accrued organ damage and the presence of capillaroscopic abnormalities. This suggests that ND might be related to chronic microvascular damage.