Immunomodulatory and Toxic Effects of Free and Liposome-encapsulated Tumor Necrosis Factor a in Rats1

ORCiD

Nejat Düzgüneş: 0000-0001-6159-1391

Department

Biomedical Sciences

Document Type

Article

Publication Title

Cancer Research

ISSN

0008-5472

Volume

50

Issue

2

First Page

375

Last Page

380

Publication Date

1-15-1990

Abstract

Tumor necrosis factor a has potent immunomodulatory and antitumor activity, but its therapeutic applications may be limited by its significant host toxicity. We showed that liposome-encapsulated recombinant human tumor necrosis factor a (rHuTNF-a) retained full anticellular activity in vitro. We then assessed the immunomodulatory and toxic effects of two different doses of i.v. free or liposome-encapsulated rHuTNF-a in normal rats. Both free and liposome-encapsulated rHuTNF-a significantly enhanced alveolar macrophage- and blood monocyte-mediated interleukin 1 release and tumor cell lysis, as well as natural killer cell cytotoxicity, when compared to buffer-treated controls. However, administration of rHuTNF-a in liposomes substantially reduced tumor necrosis factor α-mediated toxicity. Animals receiving liposome-encapsulated rHuTNF-a showed significantly less tissue injury, gastric retention, and circulating leukocyte shifts than animals receiving free rHuTNF-a. In addition, liposome-based delivery significantly increased lung and liver uptake of rHuTNF-a. Therefore, liposome-encapsulated rHuTNF-a retains immunomodulatory activity, significantly reduces toxic inflammatory effects, and may allow targeting of tumor necrosis factor a to selected organs after i.v. administration. © 1990, American Association for Cancer Research. All rights reserved.

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