Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses

Kouokam, Joseph Calvin; Lasnik, Amanda B.; Palmer, Kenneth E.

To validate the use of a murine model, we evaluated the toxicological effects of GRFT on PMBCs purified from mouse blood samples, in light of data described in our previous work on human PBMCs and cervico-vaginal cell lines [12] . As shown above, purified mPBMCs were not, or only moderately, affected by high concentrations of GRFT, in terms of viability and mitogenicity. In addition, IL-1b, IL-10 and TNF-α amounts in mPBMC culture supernatants were not altered by GRFT at concentrations of up to 4 µM. IL-6 concentrations were not affected by 1 µM GRFT, although a transient and moderate increase was observed after treatment with 4 µM at one day after treatment. These data indicate that GRFT does not boost release of the above four cytokines in mPBMCs, corroborating our previous observations that this lectin induces only minimal changes in the secretion of 27 cytokines and chemokines by human PBMCs, as assessed by multiplexed immunoassays [12] . Collectively, these findings suggested mouse to be a valid model for toxicological assessment of GRFT.