Immunomodulation human studies

M. J. Schultz, J. Kesecioglu, T. Van Der Poll (2004). Immunomodulating properties of macrolides animal and human studies. Curr. Med. Chem. Anti-Inf. Ag. 3 101-107. 

Indeed, human studies indicate that specific probiotic strains can reduce symptoms of IBS through immunomodulation (Kajander et ah, 2008 O Mahony et ah, 2001) and may have promise for the treatment of... 

A variety of other clinically important infections, such as brucellosis, listeriosis, salmonellosis, and various Mycobacterium infections, are of interest as these are often localized in organs rich in MPS cells. Liposome encapsulation has been demonstrated to improve therapeutic indices of several drugs in a number of infectious models. The natural avidity of macrophages for liposomes can also be exploited in the application of the vesicles as carriers of immunomodulators to activate these cells to an microbicidal, antiviral, or tumoricidal state. These studies were recently reviewed by Emmen and Storm (1987), Popescu et al. (1987), and Alving (1988). In addition to the treatment of "old" infectious diseases, the concept of MPS-directed drug delivery is of considerable interest for the therapy AIDS, possibly enabling control of human immunodeficiency virus replication in human macrophages. 

The sterols and sterolins in rice bran are potent immunomodulators. The best response was obtained with a 100 1 sterol/sterolin mixture that demonstrated T-cell proliferation from 20% to 920% and active cell antigens after four weeks in human subjects (Bouic et al, 1996). Another in vitro experimental study with sterol/sterolins, demonstrated a significant increase in cytokinines, interleukin-2 and y-interferon between 17% and 41 % in addition to an increase in natural killer cell activity. These experiments (Bouic et al, 1996) prove that sterol/sterolins are potent immunomodulators with important implications for the treatment of immune dysfunction. Rice bran products are excellent dietary supplements for the improvement of immune function. It is probable that the effects of rice bran on diabetes, CVD and cancer all result from improved immune function. 

A single study in animals reported no effect in the splenic natural killer cell activity in rats orally exposed to 27.1 mg/kg/day 1,2-dimethylhydrazine (Locniskar et al. 1986). However, in mice injected with 75 mg/kg/day 1,1-dimethylhydrazine, a decreased T helper cell count was observed (Frazier et al. 1991). In vitro studies have reported that 1,1-dimethylhydrazine induces immunomodulation (enhancing some immune functions while diminishing others) in mouse lymphocytes and splenocytes (Bauer et al. 1990 Frazier et al. 1992). These data are limited, but suggest that humans exposed to hydrazines may be at risk of developing immunological effects. 

The studies mentioned above indicate that bromelain has a certain cytotoxic potential. It remains an open question whether the observed antineoplastic effects of bromelain preparations reside in the proteolytic enzyme or in some or more other components of the mixture. Before the work of Maurer et al. [104] and of Batkin et al. [105], the antitumor activity of bromelain was explained primarily by its fibrinolytic and platelet aggregation inhibitory activity, which is believed to interfere with the fibrin and coagulation features of tumor cells [2], More recently, Desser and Rehberger [107] demonstrated that bromelain stimulates the production of alpha tumor necrosis factor in human peripheral blood mononuclear cell cultures in a time-dependent manner. Immunomodulation, especially the release of cytokines, is believed to be responsible for the possible therapeutic potential of bromelain. However, further experimental evidence is necessary, first, to prove the antineoplastic action of the proteolytic enzyme, and second, to demonstrate that bromelain in vivo is a valuable therapeutic agent in humans. 

Compelling evidence demonstrates that CIA targets and modulates specific components of the innate and adaptive immune system. We will review animal studies as well as pilot studies in humans and discuss some unanswered questions on immunomodulation. All of which, should be addressed through additional basic research and well-designed human intervention studies. 

In clinical studies of Szmigielski (1982), P. granulosum KP-45 was shown to display immunomodulating, antineoplastic and antiviral effects, which were associated with the activation of monocyte-macrophage system, induction of interferon synthesis and/or activation of killer cells. Stimulation of interferon synthesis was also observed in human tissue cultures. The author suggested that these effects are mediated by the cell wall components, in particular, by peptidoglycans and teichoic acids. 

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