Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM

Park, Hae-Ran; Jo, Sung-Kee; Jung, Uhee; Yee, Sung‐Tae

doi:10.1002/ptr.2255

Cited by 23 publications

(24 citation statements)

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“…Consistent with our findings, some reports have shown that aging increases IFN-γ production [30-34]. In contrast, other reports have shown that aging reduces IFN-γ production in mice [35-37], whereas Kovacs et al . reported that IFN-γ production did not differ between young and aged mice with both sham and experimental burn injury [38].…”

Section: Discussionsupporting

confidence: 92%

Persistent inflammation and T cell exhaustion in severe sepsis in the elderly

et al. 2014

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IntroductionSepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis.MethodsFifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (≥65 years) and adult (18–64 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (6–8 weeks) and aged (20–22 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7 days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured.ResultsThe survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P < 0.05). Serum IL-6 levels in elderly sepsis patients and aged septic mice were persistently higher than those in adult patients and young septic mice. Expression of negative co-stimulatory molecules in CD4+ T cells in the spleen, lymph nodes, and peripheral blood was significantly higher in aged mice than in young mice (P < 0.01). Ex vivo stimulation decreased CD25 expression, IL-2 production, and proliferation to a greater extent in CD4+ T cells from elderly patients and aged septic mice than in those from adult patients and young septic mice. Elderly patients demonstrated increased detection of gram-negative bacteria at days 14–16 and 28–32 after sepsis (P < 0.05).ConclusionsPersistent inflammation and T cell exhaustion may be associated with decreased survival in elderly patients and mice after sepsis.

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Section: Discussionsupporting

confidence: 92%

Persistent inflammation and T cell exhaustion in severe sepsis in the elderly

et al. 2014

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“…Taken together, these data would suggest that lymphocytes from old donors would be impaired in their capacity to stimulate antigen presenting cells to produce certain cytokines such as IL-12 p70, which could result in low cytokine release, including IL-1, by monocyte-macrophages. Indeed, our data and that of others in splenocytes have found decreased ConAstimulated levels of IL-12 p70 and IL-1 in old mice (Khansari and Gustad 1991;Park et al 2008). However, in the present results the very old mice showed increased IL-1α and IL-1β in response to this mitogen.…”

Section: Discussioncontrasting

confidence: 60%

Preserved ex vivo inflammatory status and cytokine responses in naturally long-lived mice

Arranz

Lord

Fuente

2010

AGE

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Preserved immune cell function has been reported in mice that achieve extreme longevity. Since cytokines are major modulators of immune responses, we aimed to determine the levels of 21 cytokines secreted ex vivo by peritoneal leukocytes cultured under basal- and mitogen- (conconavalin A (ConA) and LPS) stimulated conditions in middle-aged (44 ± 4 weeks), old (69 ± 4 weeks), very old (92 ± 4 weeks), and extreme long-lived (125 ± 4 weeks) ICR (CD1) female mice. The secretion of cytokines was measured by multiplex luminometry. Increased basal levels of proinflammatory IL-1β, IL-6, IL-12 (p70), IFN-γ, and TNF-α were seen in the old and very old animals, accompanied by decreased IL-10. In contrast, the extreme long-lived mice maintained the overall cytokine profile of middle-aged mice, though the basal secretion of IL-2, IL-9, IL-10, IL-13, and IL-12 (p40) was raised. Under LPS- and/or ConA-stimulated conditions, leukocytes from old and very old animals showed a significantly impaired response with respect to secretion of Th1 cytokines IL-3, IL-12p70, IFN-γ, and TNF-α; Th2 cytokines IL-6, IL-4, IL-10, and IL-13; and the regulatory cytokines IL-2, IL-5, and IL-17. Extreme long-lived mice preserved the middle-aged-like cytokine profile, with the most striking effect seen for the IL-2 response to ConA, which was minimal in the old and very old mice but increased with respect to the middle-aged level in extreme long-lived mice. Chemokine responses in regard to KC, MCP-1, MIP1β, and RANTES were more variable, though similar secretion of LPS-induced KC and MCP-1 and ConA-induced MCP-1, MIP-1β, and RANTES was found in long-lived and middle-aged mice. Thus, extreme long-lived animals showed only a minimal inflammatory profile, much lower than the old and very old groups and also lower than the middle-aged, which is likely mediated by the increase of anti-inflammatory cytokines such as IL-10. This was coupled to a robust response to immune stimuli across an appropriated Th1/Th2 and regulatory cytokine secretion, which seems to be a factor contributing to the preserved immune response reported in very long-lived animals and thus to their extended longevity.

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“…13 We also investigated the effect of HemoHIM on a restoration of the immune functions that had been impaired in aged mice. 19 In our previous study, we showed that HemoHIM accelerated the recovery of immune cells in mice treated with cyclophosphamide, which is a well-known chemotherapy agent. 20 Although HemoHIM alone did not directly kill the cancer cells (data not shown), our results showed that HemoHIM administration enhanced the therapeutic efficacy of IR in melanoma-bearing mice.…”

Section: Discussionmentioning

confidence: 96%

HemoHIM Enhances the Therapeutic Efficacy of Ionizing Radiation Treatment in Tumor-Bearing Mice

Park

et al. 2010

Journal of Medicinal Food

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Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

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Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM

Cited by 23 publications

References 50 publications

Persistent inflammation and T cell exhaustion in severe sepsis in the elderly

Persistent inflammation and T cell exhaustion in severe sepsis in the elderly

Preserved ex vivo inflammatory status and cytokine responses in naturally long-lived mice

HemoHIM Enhances the Therapeutic Efficacy of Ionizing Radiation Treatment in Tumor-Bearing Mice

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