Aging enhances lymphocyte cytokine defects after injury

Plackett, Timothy P.; Schilling, Eric M.; Faunce, Douglas E.; Choudhry, Mashkoor A.; Witte, Pamela L.; Kovacs, Elizabeth J.

doi:10.1096/fj.02-0452fje

Cited by 54 publications

(33 citation statements)

References 58 publications

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“…In animal models, aged mice have a higher mortality rate than young adult mice following 15% TBSA [108]. Aged mice also demonstrate significant decreases in DTH responses, Con A-stimulated splenocyte proliferation, and increases in IL-4 and IL-10 production suggesting a shift to a Th2 immune response [109]. Several studies were performed looking at the immune response following burn injury in young adult and aged mice.…”

Section: Burn and Co-morbidity Factorsmentioning

confidence: 99%

Sex differences and estrogen modulation of the cellular immune response after injury

Bird¹,

Karavitis²,

Kovacs³

2008

Cellular Immunology

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Cell-mediated immunity is extremely important for resolution of infection and for proper healing from injury. However, the cellular immune response is dysregulated following injuries such as burn and hemorrhage. Sex hormones are known to regulate immunity, and a well-documented dichotomy exists in the immune response to injury between the sexes. This disparity is caused by differences in immune cell activation, infiltration, and cytokine production during and after injury. Estrogen and testosterone can positively or negatively regulate the cellular immune response either by aiding in resolution or by compounding the morbidity and mortality. It is apparent that the hormonal dysregulation is dependent not only on the type of injury sustained but also the amount of circulating hormones. Therefore, it may be possible to design sex-specific therapies to improve immunological function and patient outcome.

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Section: Burn and Co-morbidity Factorsmentioning

confidence: 99%

Sex differences and estrogen modulation of the cellular immune response after injury

Bird¹,

Karavitis²,

Kovacs³

2008

Cellular Immunology

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“…This improved survival was accompanied by a diminution in the serum levels of IL-6 . Additionally, we have reported that estrogen treatment partially restored the delayed-type hypersensitivity response , a systemic cellular immune response previously described to be markedly attenuated in aged mice after burn injury (Kovacs et al, 2002;Plackett et al, 2003).…”

Section: Discussionmentioning

confidence: 68%

Aging and estrogen: Modulation of inflammatory responses after injury

Gómez

Plackett

Kovacs

2007

Experimental Gerontology

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Aged subjects have a poor prognosis after traumatic injury and, regardless of the type of injury, they have slower recoveries and suffer more complications than their younger counterparts. The agedependent responses may be influenced by the hyper-inflammatory state observed in the aged prior to injury, including elevated levels of interleukin-6 (IL-6). Physiological levels of estrogen are beneficial to the immune system, due, in part, to the hormone's ability to attenuate aberrant production of pro-inflammatory cytokines. Using two independent injury models, we have found increased mortality and elevated serum levels of IL-6 in aged mice, when compared to young animals (p<0.05). In parallel studies, groups of aged mice given estrogen (17β-estradiol) prior to scald burn, had significantly improved survival (p<0.05) and lowered serum . Multiple cellular mechanisms may be involved in mediating the beneficial effects of estrogen on inflammatory and immune responses in aged individuals who sustain an injury. These mechanisms are discussed herein.

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“…1 The lack of an adequate amount of Th1 cytokines shortly after injury in the aged mice may parallel the increased incidence of sepsis and death that occurs in aged burn patients. 22 Therefore, altered lymphocyte response observed in healthy aged individuals may be a contributing factor to increased mortality. SAMP8 mice show markedly low NK activity, in vitro anti-SRBC antibody responses, cell proliferation, and IL-2 production, as early as two months after birth.…”

Section: Discussionmentioning

confidence: 99%

“…Since an adequate amount of Th1 cytokines is critical to host defense in the aged animals, 22 the supplementation with nanonized black soybean might provide a benefi cial effect by favoring Th1 response in SAMP8 mice.…”

Section: Discussionmentioning

confidence: 99%

Nanonized black soybean enhances immune response in senescence-accelerated mice

Chan

Wu²,

Chan³

et al. 2009

IJN

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Soy isofl avones may have applications in cancer prevention and anti-infl ammation, therefore this study was conducted to investigate the effect of dietary supplementation with black soybean on the immune response in the senescence-accelerated-prone mice (SAMP8) and -resistant mice (SAMPR1, as controls). The mechanism of isofl avones was also investigated. Six-month-old male SAMP8 and SAMR1 mice were divided into the control groups and experimental groups supplemented with nanonized (Nano-soy) or microparticled (Micro-soy) black soybeans (n = 8/group), respectively for 12 weeks. Human peripheral blood mononuclear cells (PBMC) and murine splenocytes were stimulated with mitogens and cytokines were determined by reverse transcriptase-polymerase chain reaction and/or ELISA. The results showed that body weight, food intake, and relative weights of organs did not differ among the SAMP8 control and experimental groups. Isofl avone (daidzin and genistin) intake was higher in the Nano-soy group than the Micro-soy group. The lymphoproliferation and production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in the Nano-soy group had a signifi cantly higher (P Ͻ 0.05) than those in the control and Micro-soy groups. The Nano-soy supplemented mice reached these cytokine levels similar to SAMR1 mice. This result was consistent with the in vitro data that daidzein (a metabolite of daidzin), at a concentration of 10 μM, increased IL-2, IL-4, and IFN-γ production from phytohemagglutinin-stimulated PBMC (P Ͻ 0.05). However at higher concentrations (Ͼ50 μM), daidzein only reduced IL-10 and IFN-γ levels, whereas genistein reduced levels of the IL-2, IL-4, IL-10, IFN-γ mRNA and protein and these results suggest that the Nano-soy supplementation improved immune response in SAMP8 mice which may be attributable to higher daidzin content in the black soybean preparation.

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Aging enhances lymphocyte cytokine defects after injury

Cited by 54 publications

References 58 publications

Sex differences and estrogen modulation of the cellular immune response after injury

Sex differences and estrogen modulation of the cellular immune response after injury

Aging and estrogen: Modulation of inflammatory responses after injury

Nanonized black soybean enhances immune response in senescence-accelerated mice

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