Intrauterine group A streptococcal infections are exacerbated by prostaglandin E2.

Streptococcus pyogenes (Group A Streptococcus; GAS) is a major cause of severe postpartum sepsis, a re-emerging cause of maternal morbidity and mortality worldwide. Immunological alterations occur during pregnancy to promote maternofetal tolerance, which may increase the risk for puerperal infection. PGE2 is an immunomodulatory lipid that regulates maternofetal tolerance, parturition, and innate immunity. The extent to which PGE2 regulates host immune responses to GAS infections in the context of endometritis is unknown. To address this, both an in vivo mouse intrauterine (i.u.) GAS infection model and an in vitro human macrophage-GAS interaction model were used. In C57BL/6 mice, i.u. GAS inoculation resulted in local and systemic inflammatory responses and triggered extensive changes in the expression of eicosanoid pathway genes. The i.u. administration of PGE2 increased the mortality of infected mice, suppressed local IL-6 and IL-17A levels, enhanced neutrophilic inflammation, reduced uterine macrophage populations, and increased bacterial dissemination. A role for endogenous PGE2 in the modulation of antistreptococcal host defense was suggested, because mice lacking the genes encoding the microsomal PGE2 synthase-1 or the EP2 receptor were protected from death, as were mice treated with the EP4 receptor antagonist, GW627368X. PGE2 also regulated GAS-macrophage interactions. In GAS-infected human THP-1 (macrophage-like) cells, PGE2 inhibited the production of MCP-1 and TNF-α while augmenting IL-10 expression. PGE2 also impaired the phagocytic ability of human placental macrophages, THP-1 cells, and mouse peritoneal macrophages in vitro. Exploring the targeted disruption of PGE2 synthesis and signaling to optimize existing antimicrobial therapies against GAS may be warranted.

Ocular manifestations in Iranian patients referred to rheumatology clinics from 2018 to 2020.

AIM: Autoimmune diseases are presented with many signs and symptoms. Eyes are commonly involved in these diseases. This study aimed to estimate the prevalence of different ophthalmological complications in patients with and without immune-mediated rheumatological diseases. METHODS: Patients who were referred to Kermanshah's rheumatologic clinics by an ophthalmologist from 2018 to 2020 for a rheumatologist visit were included. A checklist for extracting data from medical files; containing symptoms, organ involvement, ocular diseases diagnosed by an ophthalmologist, rheumatologic diseases diagnosed by a rheumatologist, lab tests, and disease progression was created. After we evaluated the medical data, we found that 54 patients out of 106 were diagnosed to have immune-mediated rheumatological diseases. Patients were divided into two groups; the first group included patients with diagnosed immune-mediated rheumatologic disease and ophthalmic complications; patients with no known immune-mediated rheumatological disease were considered the second group. The obtained information was analyzed using statistical tests. RESULTS: One hundred and six patients participated in this study, 67% of whom were females. The most common ocular symptom was blurred vision (49%). Involvement of both eyes (43.4%) was more common than single left or right eye involvement. The most common ophthalmic disease was anterior uveitis (35.8%). The most common rheumatologic disease was Behçet's disease (21.7%). Hypertension and hypothyroidism were the most common comorbidities; 36.7% of the patients had skin and mucous involvement, and 37.7% had joint involvement. In follow-up of the ophthalmic symptoms, most patients were controlled partially. Ophthalmic diseases, laboratory tests, joint involvement, skin and mucous involvement, and lung involvement were associated with rheumatologic diseases. CONCLUSION: Early diagnosis of ocular involvement in rheumatologic diseases is crucial to prevent adverse complications. The results can be beneficial for a better perception of ophthalmic symptoms and diseases among patients with autoimmune diseases.