Effects of Testosterone, 17β‐Estradiol, and Downstream Estrogens on Cytokine Secretion from Human Leukocytes in the Presence and Absence of Cortisol

Janele, David; Lang, Thomas; Capellino, Silvia; Cutolo, Maurizio; Silva, José António Pereira da; Straub, Rainer H.

doi:10.1196/annals.1351.015

Cited by 57 publications

(57 citation statements)

References 28 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…L J MA and others . Modulation of DTH by gender, OVX and E2 metabolized to several hydroxyestrogens (reviewed in Mueck et al 2002), and 4-and 16a-hydroxyestrogens are considered to be pro-inflammatory (Janele et al 2006), while 2-hydroxyestrogens are considered to be anti-inflammatory (Janele et al 2006). Progesterone is also anti-inflammatory under some circumstances, contributing to tolerance of the embryo during pregnancy (Zhao et al 2002), and likewise testosterone has been shown to reduce some immune responsivity .…”

Section: Discussionmentioning

confidence: 99%

Local cytokine levels associated with delayed-type hypersensitivity responses: modulation by gender, ovariectomy, and estrogen replacement

Lisa

Guzmán

Muller

et al. 2007

Journal of Endocrinology

View full text Add to dashboard Cite

It is well established that females mount stronger immune responses than males, but only very little is understood about the underlying mechanisms. We have analyzed local cytokine differences among intact females, those that had been ovariectomized (OVX), those receiving estrogen replacement after OVX, and males, both before and after production of delayed-type hypersensitivity (DTH) responses. We report confirmation of a much larger DTH response in females versus males. However, OVX resulted in an even larger response, while estrogen replacement resulted in a smaller response when compared with intact females. In animals exposed for the first time to an antigen (without a DTH response), OVX increased interleukin-6 (IL-6) and estrogen replacement after OVX suppressed IL-6. Of the cytokines that differed between males and females exposed for the first time to an antigen, only IL-6 was higher in females versus males when exposure to antigen occurred for the second time (when the DTH response occurs). Analysis of cytokines with OVX and estrogen replacement after a second exposure to antigen showed that IL-6 did not significantly change. Levels of IL-4; Regulated upon Activation, Normal T-cell Expressed; and Secreted; and thrombopoietin, however, correlated with the DTH response, suggesting direct or indirect positive regulation by estrogen. These results suggest an important role for both IL-6 and IL-4 in determining the degree of DTH response, with IL-6 (which appears negatively regulated by estrogen) increasing and IL-4 (which appears positively regulated by estrogen) decreasing the response. The results further suggest that IL-6 may play a role in predisposing to a larger DTH response, while IL-4 levels seem more important during an active response.

show abstract

Section: Discussionmentioning

confidence: 99%

Local cytokine levels associated with delayed-type hypersensitivity responses: modulation by gender, ovariectomy, and estrogen replacement

Lisa

Guzmán

Muller

et al. 2007

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Testosterone has been reported to have immune suppressive effects 4,[8][9][10][11] . In the mouse, T reduces macrophage expression of toll-like receptor 4, a trigger for inflammation and innate immunity 8 .…”

Section: Biological Studies Supporting Testosterone Suppression Of Inmentioning

confidence: 99%

“…In the mouse, T reduces macrophage expression of toll-like receptor 4, a trigger for inflammation and innate immunity 8 . Testosterone has been shown to suppress interleukin 2 (IL-2), IL-4, and IL-10 production by human leukocytes in vitro, while estradiol stabilized or increased immune stimuli-induced secretion of these and other cytokines 9 . Testosterone also stimulated apoptosis of human bone marrow-derived macrophages by a mechanism involving caspase-3, caspase-8, and poly(ADP-ribose) polymerase 10 .…”

Section: Biological Studies Supporting Testosterone Suppression Of Inmentioning

confidence: 99%

Hypothalamic-Pituitary-Gonadal Axis Hormones and Male Rheumatoid Arthritis: Novel Perspectives

Masi¹,

Chatterton²,

Aldag³

2009

J Rheumatol

View full text Add to dashboard Cite

“…Interestingly, the percentages of IL-2-and IFN-γ-positive lymphocytes and TNF-α-producing monocytes were not altered by testosterone [11]. In contrast, Janele et al (2006) showed that joint treatment with cortisol and testosterone inhibited production of IL-2, IL-4, IL-10 and reduced the secretion of TNF-α and IFN-γ by human leukocytes, although, no changes were found with treatment with testosterone only [12]. Some of the differences cited above may be due to the cell type involved, hormone concentration or be specie-specific, nevertheless, they strongly indicate that sex hormones are able to induce immunomodulation.…”

Section: Introductionmentioning

confidence: 92%

Differences in age modulates neutrophils function

Lagranha¹,

Alba-Loureiro²,

Silva³

et al. 2014

ABC

View full text Add to dashboard Cite

The sexual maturation in all mammals is the period in which the quiescent gonads are activated by gonadotropins from anterior pituitary, increasing the secretion of sexual hormones. Sexual maturation is also related with the development of several other body features such as body mass and maturation of the circulatory, skeletal and hematopoietic systems. The aim of the present study was to evaluate the function of neutrophils submitted to in vivo lower and higher concentration of testosterone (sexually immature: 60 days and sexually mature: 90 days). Using different approaches we evaluated cell viability and function and gene expression in rat neutrophils from 60 and 90 days-old animals. Neutrophils from 90 days-old rats showed a decrease in phagocytic and fungicidal capacity, without change in cellular viability. Additionally, we verified that sexual maturation induced increase in production of reactive oxygen and nitrogen species (RONS) and also in TNF-α, IL-6 and IL-10 cytokines. In conclusion, our data suggest that increase in testosterone levels induced significant alteration in neutrophil function, impairing phagocytic capacity.

show abstract

Effects of Testosterone, 17β‐Estradiol, and Downstream Estrogens on Cytokine Secretion from Human Leukocytes in the Presence and Absence of Cortisol

Cited by 57 publications

References 28 publications

Local cytokine levels associated with delayed-type hypersensitivity responses: modulation by gender, ovariectomy, and estrogen replacement

Local cytokine levels associated with delayed-type hypersensitivity responses: modulation by gender, ovariectomy, and estrogen replacement

Hypothalamic-Pituitary-Gonadal Axis Hormones and Male Rheumatoid Arthritis: Novel Perspectives

Differences in age modulates neutrophils function

Contact Info

Product

Resources

About