This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tandon, P. Articles by Sone, S. Search for Related Content PubMed PubMed Citation Articles by Tandon, P. Articles by Sone, S.

Lack of Production of Interleukin 1 by Human Blood Monocytes Activated to the Antitumor State by Liposome-encapsulated Muramyl Tripeptide¹

3rd Department of Internal Medicine, The University of Tokushima School of Medicine, Kuramoto-cho, Tokushima, Japan

Previously human blood monocytes were shown to become tumoricidal when treated in vitro with lipopolysaccharide, muramyl dipeptide analogue, or liposomes containing muramyl dipeptide analogue. In this study the ability of human blood monocytes activated to the antitumor state by these macrophage activators to produce interleukin 1 (IL-1) was examined. Blood monocytes separated by centrifugal elutriation did not release IL-1 into the culture supernatant but elaborated IL-1 maximally within 24 h after treatment with lipopolysaccharide or desmethyl muramyl dipeptide. In contrast, they did not elaborate IL-1 when rendered tumoricidal by muramyl tripeptide phosphatidylethanolamine (MTP-PE) encapsulated in multilamellar vesicle liposomes composed of phosphatidylcholine and phosphatidylserine in a molar ratio of 7:3. IL-1 rich supernatants that induced thymocyte proliferation were not adsorbed or destroyed by the liposomes, and addition of supernatants from cultures of monocytes treated with liposome-MTP-PE to IL-1 rich supernatants did not inhibit thymocyte proliferation. MTP-PE in liposomes composed of phosphatidylserine or phosphatidylcholine or both in various molar ratios also did not induce IL-1 production by monocytes. These results indicate that MTP-PE encapsulated in liposomes may be useful in in situ activation of human blood monocytes to the antitumor state for destruction of clinical micrometastases because MTP-PE encapsulated in liposomes does not stimulate production of IL-1, which is responsible for undesirable side effects such as fever and granulomatous reactions.

¹ Research sponsored by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture, by a Grant-in-Aid from the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and by a grant from the Japanese Foundation for Multidisciplinary Treatment of Cancer.

² To whom requests for reprints should be addressed.

Received 2/ 4/86. Accepted 6/19/86.