REGULATORY EFFECTS OF HUMAN RECOMBINANT IL-6 ON NATURAL KILLER CELL ACTIVITY OF HUMAN FETAL SPLEENS

In the present study it was proved first that human recombinant interleukin-6(HrIL-6) significantly augmented natural killer(NK) cell activity derived from human fetal spleens against K562 target cells in a 4 hours 51Cr release assay. The enhancement of NK activity with 24 hours preincubation in HrlL-6 was dose-dependent, and significantly higher than that of fresh NK cells and controls cultured with RPMI-1640 medium alone (P<0.001). We also found that IL-6 was able to augment NK activity from different fetal spleens at 20 to 40 weeks of gestation (up to 2.24 to 2.78 times), and no difference of NK activity of fetal splenocytes treated by HrIL-6 was observed between different fetal age (32.3% to 45.4%, P>0.05). Furthermore, IL-6-augmented NK activity of fetal splenocytes was very similar to adult levels (P>0.05). These finding strongly indicated that IL-6 plays an important role in the development of NK cell function during the gestational period, suggesting that IL-6 may be of importance in the regulation of host defense mechanisms against malignancies and viral diseases.

Pharmacological Investigation on the Qi-Invigorating Action of Schisandrin B: Effects on Mitochondrial ATP Generation in Multiple Tissues and Innate/Adaptive Immunity in Mice

Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory has shown that the Qi-invigorating action of Chinese tonifying herbs is linked to increased mitochondrial ATP generation and an enhancement in mitochondrial glutathione redox status. To explore whether Sch B can exert Qi-invigorating actions across various tissues, we investigated the effects of Sch B treatment on mitochondrial ATP generation and glutathione redox status in multiple mouse tissues ex vivo. In line with TCM theory, which posits that Zheng Qi generation relies on the Qi function of the visceral organs, we also examined Sch B’s impact on natural killer cell activity and antigen-induced splenocyte proliferation, both serving as indirect measures of Zheng Qi. Our findings revealed that Sch B treatment consistently enhanced mitochondrial ATP generation and improved mitochondrial glutathione redox status in mouse tissues. This boost in mitochondrial function was associated with stimulated innate and adaptive immune responses, marked by increased natural killer cell activity and antigen-induced T/B cell proliferation, potentially through the increased generation of Zheng Qi.

Differential Effects of Yin- and Yang-Chinese Tonifying Herbs on Innate and Adaptive Immunity

The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).

Effects of HHV-6 Infection in Vitro on Cytokines Induction and NK Activity of Peripherial Blood Mononuclear Cells

Three Nanjing local strains (CN5, CN8, CN10) of human herpesvirus 6 (HHV-6] had been isolated and identified by electronmicroscopy, antibody reactions with IFA and specific PCR. The purpose of this paper was to study effects on cytokines synthesis and NK activity of peripheral blood mononuclear cells(PBMC) in vitro post infection of human herpesvirus 6. PBMCs cultural supernatants were collected at different hours post infection. Cytokines such as TNF-α, IFN-α and IL-8 could be detected as early as 24 h post infection, plateaued at 48h, and then decreased gradually. The levels of these cytokines in infected PBMCs supernatants were markedly higher than those in uninfected ones, but the IL-6 level was lower than that of uninfected one. These differences between infected and uninfected groups were all significant(P<0.05). There were no differences in the induction of TNF-α, IFN-α and IL-8 between the local strain CN8 and GS strain (all P>0.05), while the inhibition of IL-6 production induced by GS strain was more prominant than that induced by CN8 (P<0.05). It was also found that NK activity was augmented at 24h post infection, which was more striking in CN8 strain infection group than in GS strain infection group (P<0.05), after then, it was gradually decreased. From these reults, it could be inferred that the increase of cytokines synthesis and augmentation of NK activity were associated with convalescence and pathogenicity of the HHV-6 infection. GS strain, which belongs to groups A, disturbed the function of human immunity more remarkably than the local strain CN8, which belongs to group B.

The Effects of Astragalus membranaceus and Tripterygium hypoglaucum on NK Activity in Systemic Lupus Erythematosus

The natural killer cell activity of peripheral blood mononuclear cells from 28 patients withsystemic lupus erythematosus was measured using enzyme-release assay. The patients exhibited obvi-ously decreased natural killer cell activity compared with the healthy subjects in the control group. Thenatural killer cell dysfonction was related to steroidal therapy, but not to three auto-antibodies. The re-lease of a soluble natural killer cytotoxic factor by the peripheral blood mononuclear cells was tested bycytotoxicity assay induced in K256 cells. This release was significantly lower in the test group than in thecontrol group. Pre-incubation of peripheral blood mononuclear cells with Astragalus membranaceus andTripterygium hypoglaucum considerably enhanced natural killer cytotoxicity by stimulating the release ofsoluble cytotoxic factors.