Cortisol and proinflammatory cytokine profiles in type 1 (reversal) reactions of leprosy.

PURPOSE: Cortisol levels in the circulation and at the sites of peripheral inflammation regulate type 1 (Reversal) reactions in leprosy akin to delayed type hypersensitivity reactions (DTH). In this study we determine the extent to which the differential mRNA expression of genes encoding cortisone-cortisol shuttle enzymes (11 ß hydroxysteriod dehydrogenase I & II (11 ß HSD I & II)), circulatory levels of proinflammatory cytokines (IL-6, IL-7, IP-10, IL-17F, IL-23, TNF-α, IL-1ß, PDGF BB and CRP) and cortisol are associated with development of type 1 reactions in leprosy. METHODS: Urine, blood and incisional skin biopsy samples from site of lesions were collected from 49 newly diagnosed untreated leprosy cases in T1R and 51 cases not in reaction (NR). mRNA expression levels of genes encoding 11 ß HSD I & II in skin biopsy samples were determined by realtime PCR. Cortisol levels from the lesional skin biopsies, serum and urine samples and serum proinflammatory cytokine levels were measured using ELISA. RESULTS: The mean expression ratios of 11 ß HSD I & II are significantly lower in leprosy cases with T1R when compared to the NR leprosy cases. Cortisol levels in lesional skin biopsies and in urine are significantly lower (p=0.001) in leprosy cases with T1R. Serum cytokine levels of IP-10, IL-17F, IL-IL-6 and TNF-α are significantly higher (p<0.05) in leprosy cases with T1R when compared the NR leprosy cases. CONCLUSION: Our study indicated an association of urinary and lesional skin cortisol levels with the manifestation of T1R in leprosy. IP-10, IL-17F, IL-6 and TNF-α can be potential prognostic serological markers and gene expression markers for early detection of type 1 reactions in leprosy.

Evaluation of hypothalamic-pituitary-adrenal axis in patients with atopic dermatitis.

BACKGROUND: Most of the research on atopic dermatitis (AD) has focused on the pathophysiological role of the immune system in AD, and the role of endocrine signals in the pathology of AD has not been explored. Current research has shown a link between the neuroendocrine and immune functions. AIM: The aim was to measure the serum basal cortisol levels and cortisol levels following a low-dose ACTH stimulation test in patients with AD before and after treatment with corticosteroids. METHODS: Three groups of patients with AD were evaluated: mild, moderate, and severe. Basal cortisol levels following an ACTH stimulation test were measured before and after treatment with topical steroids when an improvement in the disease activity by 75% as determined by the SCORAD index was observed. RESULTS: Eighteen patients of the severe group at baseline showed an impaired hypothalamic-pituitary-adrenal (HPA) axis with cortisol levels <250 nmol/l during their first visit. A total of 13 of 18 patients regained their HPA axis activity when the baseline cortisol was measured after using topical corticosteroids which resulted in 75% improvement in the disease activity. CONCLUSIONS: The disease activity rather than the use of topical corticosteroids is responsible for the low basal levels in patients with severe AD.

Adrenocortical hormones and interleukin patterns in leprosy.

The functional status of adrenocortical hormones and their relationship to the pattern of inflammatory cytokines in the lepromatous and tuberculoid poles of leprosy were investigated. Interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha plasma levels, C-reactive protein (CRP) concentrations and erythrocyte sedimentation rates (ESR) were significantly higher in LL/BL (lepromatous) leprosy patients than in control subjects. There was a significant positive correlation between IL-6 and TNF-alpha plasma levels and ESR and CRP concentrations. IL-1beta was positively correlated with ESR but not with CRP. Both baseline and stimulated adrenocorticotropic hormone and cortisol plasma levels were not different between patients and control subjects. In contrast, adrenal androgen dehydroepiandrosterone sulphate (DHEA-S) plasma levels were significantly lower in leprosy patients than in sex-matched control subjects. There was a significant inverse correlation between DHEA-S and IL-6, TNF-alpha, and CRP concentrations. This finding may be of pathogenetic significance in this disease and in other inflammatory states.

Cortisol status in different types of leprosy.

Basal plasma cortisol levels in 12 controls and 60 patients with different types of leprosy were within normal limits. They were significantly lower in multibacillary leprosy patients; this abnormality might be due to long standing stress leading to adrenal exhaustion. The plasma cortisol level significantly increased after the ACTH (Synacthen) stimulation test in all of the varieties of leprosy tested, which suggests that the adrenal reserve is maintained in such cases.

[Effects of endogenous cortisol on the function of nonspecific T-suppressors and quantitative characteristics of main subpopulations of circulating T-lymphocytes in leprosy]. / Vliianie éndogennogo kortizola na funktsiiu nespetsificheskikh T-supressorov i kolichestvennye kharakteristiki osnovnykh subpopuliatsii tsirkuliruiushchikh T-limfotsitov pri lepre.

Serum hydrocortisone levels, cellular immunity and their correlation were studied in 38 patients with lepromatous lepra in regression. 12 of them had exacerbation of specific polyneuritis. The latter condition is accompanied by a rise in hydrocortisone concentrations. Relative number of blood CD8+ lymphocytes correlated positively with hydrocortisone content, whereas the quantity of CD4+ cells correlated negatively. In patients without neurological complications in negative correlation between blood hydrocortisone and lymphocyte glucocorticoid sensitivity there was a positive relationship between nonspecific T-suppressor activity and hydrocortisone levels. The involvement of endogenic hydrocortisone in T-suppressor activity regulation in regressive lepra can help understand the role of endocrine dysfunction and stress in pathogenesis of lepra relapses.

Autosensitization to connective tissue elements and endogenous adaptation hormones in mycobacterioses.

The contribution of some adaptation hormones to the process regulating production of autoantibodies to collagen (Abc) and elastin (Abe) was studied in leprosy (37 patients) and tuberculosis (31 patients). In both mycobacterioses the Abc and Abe titers were increased and inversely correlated with endogenous cortisol levels. In leprosy the antibody titers directly correlated with the triiodothyronine (T3) levels which were significantly higher than the values in healthy controls. A new approach to research for remedies and methods of preventing and curing autosensitization to connective tissue is suggested by combining medications according to individual endocrine and immune indices.

Adreno-cortical function in leprosy.

Adreno cortical function was carried out in 43 cases of leprosy. These cases were further divided into tuberculoid, borderline, lepromatous and Lepra reaction. Serum and urinary electrolyte, urinary 17-Ketosteroid and 17-Ketogenic steroid and plasma cortisol levels were measured to assess the adrenocortical status in these different forms of leprosy. It was observed that these parameters were within normal limit in tuberculoid leprosy except low value of urinary 17-Ketogenic steroid. The borderline and Lepromatous leprosy cases revealed low values of urinary sodium, potassium and 17-Ketogenic steroid and high level of serum potassium. However, the cases of lepra reaction revealed low value of serum and urinary sodium and potassium, urinary 17-Ketogenic steroid. The basal plasma cortisol level was high in this group but it was statistically insignificant.

Adrenal cortical function and reserve in lepromatous leprosy.

22 chronic Lepromatous Leprosy patients of over 10 years duration, 17 non-reactional and 5 in reactional state who have not taken steroids as part of treatment were selected for the study. Serum cortisol was estimated by Radio-immuno-assay. Samples for basal values were collected at 8.00 A.M. Stimulated values were estimated in samples collected 8 hours after ACTH gel 40 units IM or 2 hours after 0.15 unit/kg BW Plain Insulin I.V. Basal cortisol values are: Normal controls 123.06 +/- 57.33 ng/ml. Non-reactional: 100.47 +/- 30.33 ng/ml; Reactional 141.4 +/- 43.15 ng/ml. Stimulated values are: Normal controls: 207.6 +/- 72.57 ng/ml. Non-reactional: 175.33 +/- 57.07 ng/ml, Reactional: 230 +/- 40.92 ng/ml. Basal serum cortisol in the non-reactional state is slightly lower than in normals but not statistically significant (P greater than 0.1). The basal cortisol in reactional subjects is slightly higher than in normals but not significant statistically (P greater than 0.05). The percentage rise over the basal value after stimulation test is found to be significantly low in both the reactional and non reactional states (P greater than 0.05) and also there is no statistically significant difference between these two groups (p greater than 0.5). Hence it is concluded that the Adrenal cortical reserve is low both in the non-reactional and reactional states of Lepromatous Leprosy.

Hormone profile in lepromatous leprosy. A preliminary study.

In a preliminary study, 11 male patients with lepromatous leprosy were evaluated with regard to endocrinopathy and hormonal status. Basal circulating hormone levels were estimated with a view to correlating the biochemical findings and clinical features. Thyroid hormones T3 and T4, Free Thyroxine Index (FTI), TSH, and cortisol were within normal limits, indicating that further study of these hormones would not be worthwhile. The finding of elevated levels of prolactin as well as the gonadotrophins LH and FSH, however, promises to yield more valuable information if studied in greater detail in a larger group of patients.