Sex Hormones Alter Th1 Responses and Enhance Granuloma Formation in the Lung

Tajima, Ken; Miura, Kiyonori; Ishiwata, Toshiji; Takahashi, Fumiyuki; Yoshioka, Masataka; Minakata, Kenji; Murakami, Akiko; Sasaki, Shinichi; Iwakami, Shin‐ichiro; Annoura, Takeshi; Hashimoto, Muneaki; Nara, Takeshi; Takahashi, Kazuhisa

doi:10.1159/000324295

Cited by 7 publications

(4 citation statements)

References 58 publications

(36 reference statements)

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“…These differences were reversed by E2 and progesterone when administered individually or in combination. The enrichment of pulmonary granulomatous inflammation in ovariectomized rats was validated by a more recent study [57]. These results align with a second peak in incidence of sarcoidosis in older women [58].…”

Section: Oestrogenssupporting

confidence: 64%

“…The effects of oestrogen on pulmonary granulomatous inflammation have been the subject of few studies. The enrichment of pulmonary granulomatous inflammation in ovariectomized rats was validated by a more recent study [57]. In addition, the bronchoalveolar lavage (BAL) content of ovariectomized animals was characterized by reduced macrophages and increased neutrophils, activated T cells and IFN-γ production.…”

Section: Oestrogensmentioning

confidence: 85%

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Exploring immunomodulation by endocrine changes in Lady Windermere syndrome

Holt

Miles

Inder

et al. 2019

Clinical and Experimental Immunology

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Lung disease due to nontuberculous mycobacteria (NTM) occurs with disproportionate frequency in postmenopausal women with a unique phenotype and without clinically apparent predisposing factors. Dubbed 'Lady Windermere syndrome', the phenotype includes low body mass index (BMI), tall stature and higher than normal prevalence of scoliosis, pectus excavatum and mitral valve prolapse. Although the pathomechanism for susceptibility to NTM lung disease in these patients remains uncertain, it is likely to be multi-factorial. A role for the immunomodulatory consequences of oestrogen deficiency and altered adipokine production has been postulated. Altered levels of adipokines and dehydroepiandrosterone have been demonstrated in patients with NTM lung disease. Case reports of NTM lung disease in patients with hypopituitarism support the possibility that altered endocrine function influences disease susceptibility. This paper catalogues the evidence for immunomodulatory consequences of predicted endocrine changes in Lady Windermere syndrome, with emphasis on the immune response to NTM. Collectively, the data warrant further exploration of an endocrine link to disease susceptibility in Lady Windermere syndrome.

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Section: Oestrogenssupporting

confidence: 64%

Section: Oestrogensmentioning

confidence: 85%

Exploring immunomodulation by endocrine changes in Lady Windermere syndrome

Holt

Miles

Inder

et al. 2019

Clinical and Experimental Immunology

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show abstract

“…This is chiefly because increases of Th1 due to ageing, immunosenescence and hormonal changes do not affect the Th2 mediated humoral immune response. Tajima K et al [72] have proved that the levels of Th1–type cytokines in the bronchoalveolar lavage fluid of ovariectomized rats were significantly higher than those in sham rats, while the levels of Th2–type cytokines in both bronchoalveolar lavage fluid and serum were comparable between ovariectomized and sham rats.…”

Section: Resultsmentioning

confidence: 99%

COVID–19 and Progesterone: Part 2. Unraveling High Severity, Immunity Patterns, Immunity grading, Progesterone and its potential clinical use

Shah¹

2021

Endocrine and Metabolic Science

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Severely ill COVID–19(Corona Virus Disease of 2019) patients have a hyperinflammatory condition with a high concentration of pro-inflammatory cytokines termed the cytokine storm. This milieu is reported to cause acute lung injury, oxygen deprivation, multiorgan damage, critical illness, and often death. Post SARS–CoV–2(Severe Acute Respiratory Syndrome Coronavirus 2) infection, the fight between the invading virus and the host's immune system would either terminate in recovery, with eradication of the infection and regulation of the immune system; or there would be a continuation of immune attacks even after the virus has been cleared, leading to immune dysregulation and disease. This outcome is chiefly dependent on two factors: (1) the patient's immune response, and (2) sufficiency plus efficiency of the regulator(s). Concerning the first, the present research introduces a framework based on different types of immune responses to COVID–19 along with known disease examples,and how this relatesto varying clinical outcomes and treatment needs for COVID–19 patients. About the second factor of ‘regulator(s)’, part 1 of the manuscript described in depth the regulatory role of progesterone in COVID–19.The present study investigates the two immunity patterns and the status of the regulatory hormone progesterone with respect to the two established demographic risk factors for high-severity COVID–19: male sex, and old age. The study evaluates the status of progesterone as a credible participant of immune regulationand dysregulation. It duly relates the immunity patterns to clinical outcomes and evinces indications for clinical use of progesterone in COVID–19.It proposes a clear answer to the question: why are males and old patients most likely to have critical illness due to COVID–19? The study highlights clinical domains for the use of progesterone in COVID–19. Part 2 of this research introducing the concept of immunity patterns and immunity grading. These concepts herewith provided for the clinical course of COVID–19 also applies to other hyperinflammatory conditions. Possible clinical applications of progesterone to treat critically ill COVID–19 patients will open an avenue for hormonal treatments of infections and other immune-related diseases.

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“…Early clinical observations among women with a previous diagnosis of sarcoidosis have revealed postpartum relapse as well as remission during pregnancy, suggesting that certain female reproductive and hormonal factors may reduce the disease’s activity. Based on experimental findings on enhanced granulomatous reactions after bilateral oophorectomy [ 22 , 23 ], decreases in the circulating ovarian hormones promote the development of granulomatous diseases, including sarcoidosis.…”

Section: Discussionmentioning

confidence: 99%

Age-related differences in the clinical features of ocular sarcoidosis

et al. 2018

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The distribution of age at diagnosis in ocular sarcoidosis has shifted towards the older age groups in developed countries. In systemic sarcoidosis, age-related differences in the clinical presentation, which reflect the therapeutic strategies, was reported. We retrospectively compared 100 consecutive patients from April 2010 to March 2016 who were initially diagnosed with ocular sarcoidosis by International Workshop on Ocular Sarcoidosis criteria. They were classified into elder (>65 years: 50 patients) and younger (≤65 years: 50 patients) groups by the age at diagnosis of uveitis associated with sarcoidosis. All patients received ophthalmic examination to assess the presence of seven intraocular signs and 4 laboratory parameters. Significantly fewer ocular signs (2.8 ± 1.5 and 3.6 ± 1.5; P = 0.0034) and abnormal laboratory results (1.5 ± 1.2 and 2.0 ± 1.2; P = 0.023) were detected in the elder group than in the younger group; statistical differences were found between the groups regarding the frequencies of mutton-fat keratic precipitates (40% and 64%; P = 0.012), vitreous opacities (60% and 78%; P = 0.0059), bilateral inflammation (64% and 80%; P = 0.012), and bilateral hilar lymphadenopathy between the groups (52% and 78%; P < 0.001). Multiple linear regression analysis showed negative correlations between age and number of detected ocular signs (r = −0.36, P < 0.001) and laboratory results (r = −0.20, P = 0.023). The characteristic ocular signs and abnormal laboratory results had a lower frequency in the elder patients compared with the younger patients. Probable or possible ocular sarcoidosis by the international criteria should increase with increased life expectancy in developed countries.

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Sex Hormones Alter Th1 Responses and Enhance Granuloma Formation in the Lung

Cited by 7 publications

References 58 publications

Exploring immunomodulation by endocrine changes in Lady Windermere syndrome

Exploring immunomodulation by endocrine changes in Lady Windermere syndrome

COVID–19 and Progesterone: Part 2. Unraveling High Severity, Immunity Patterns, Immunity grading, Progesterone and its potential clinical use

Age-related differences in the clinical features of ocular sarcoidosis

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