Macrophage-activating immunomodulators

The polyanions can function as chemical immunomodulators and produce a wide spectrum of effects on the immune system. It was reported that the polyanions have the capacity to activate macrophages, which may be related to their effects on the plasma membrane lipids, and to provide immuno-modulation through B-cell stimulation [8,9]. It was also observed that the antiviral, antibacterial, and antitumor activities of pyran copolymer may be mediated by the induction of interferon (IFN) production [10], macrophage activation [11], or stimulation of antibody-dependent cellular cytotoxicity... 

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. 

Fogler, W.E., Talmadge, J.E., and Fidler, I.J., The activation of tumoricidal properties in macrophages of endotoxin responder and nonresponder mice by liposome-encapsulated immunomodulators, JReticuloendothel. Soc, 33, 165, 1983. 

Encapsulation of immunomodulators, e.g. muramyl tripeptide analogues, into liposomes has been designed to stimulate host immunity [108] and can be used in combination with other treatment modalities. The systemic activation of macrophages provides an additional therapeutic modality for the eradication of cancer and cancer metastases. 

L. rhamnosus GG Immunomodulation Activates NF-kB and regulates inflammatory response in macrophages Miettinen et al. (2000)... 

There are several subspecies of IFNy determined by differential glycosylation. IFNy is the most potent immunomodulator of all IFN. IFNy is cidal to human tumor cell lines, activates monocyte/macrophages, upregulates Class II MHC expression and increases natural killer cell activity [64]. In the kidney, IFNy regulates Class I and II MHC expression in the basal state, in response to inflammatory stimuli, and after ischemia or ischemia-reperfusion renal injury [65]. 

IL-10 and IL-4 inhibit cytoldne expression in activated human monocytes, which suggests that IL-4 may inhibit the transcription of the IL-6 gene. IL-10 may inhibit the IL-6 mRNA levels posttranscriptionally, without suppressing promoter activity in human monocytes.IL-10 also inhibits the production of IL-6, IL-12, and TNFa." Reduced IL-6 levels in individuals who are exposed to chromate were reported, pointing to its possible role in negative immunomodulation. Also, nitrite (NO ) induces a decrease of LPS-stimulated IL-1 (3, IL-6, IL-8, and TNFa release from activated alveolar macrophages. ... 

Interferon alfa-2b is an immunomodulator. It causes inhibition of virus replication in virus-infected cells, suppression of cell proliferation, and such immunomodulating activities as enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of lymphocytes for target cells. It is indicated in hairy cell leukemia condylomata acuminata AIDS-related Kaposi sarcoma chronic hepatitis B chronic non-A/non-B hepatitis (hepatitis C) and malignant melanoma and follicular non-Hodgkin s lymphoma. 

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