Adjuvant Treatment Using Dialyzable Leukocyte Extract for Herpetic Keratitis

Abstract

Introduction:: The immune response to herpetic keratitis begins on the early stage of viral replication, attracting T lymphocytes to the site of lesion and producing large quantities of IFNγ. It is known that dialyzable leukocyte extract (DLE) has the ability to modulate the immune response, probably due to IFNγ production. Therefore, DLE has been used in the treatment of viral infections like herpes simplex and herpes zoster.

Purpose:: To evaluate the cytokine production profile by peripheral blood mononuclear cells (PBMC) from herpetic keratitis patients (HK-p) treated with dialyzable leukocyte extract.

Methods:: CD4, CD8, IFNγ, IL-4, perforine and granzime expression was determined by flow cytometry on PBMC from HK-p, before (BDLE) and after (ADLE) treatment with DLE and also on PBMC from healthy controls (HC).

Results:: Percentage (%) CD4+IFNγ+ T cells in HK-p BDLE= 15 vs 9 HC (p=0.01) vs 33 ADLE (p=0.02) (p= 0.009 HC vs ADLE); %CD4+ IL-4+ T cells in HK-p BDLE= 20 vs 12 HC vs 6.5 ADLE; %CD8+IFNγ+ T cells in HK-p BDLE= 23 vs 25 HC vs 50 ADLE (p=0.002 BDLE vs ADLE, p=0.008 ADLE vs HC); %CD8+IL-4+ T cells in HK-p BDLE= 7 vs 10 HC vs 10 ADLE; %CD8+IL-4+ T cells= 7 vs 23 CD8+IFNγ+ T cells in HK-p BDLE (p=0.005); %CD8+IL-4+ T cells= 10 vs 50 CD8+IFNγ+ T cells in HK-p ADLE (p=0.003); %CD4+Granzime+ T cells in HK-p BDLE= 9.5 vs 9.4 HC vs 10.7 ADLE; %CD4+Perforine+ T cells in HK-p BDLE= 5.7 vs 1.1 HC vs 9 ADLE; %CD4+Granzime+Perforine+ T cells in HK-p BDLE= 8.1 vs 2.7 HC vs 10.8 ADLE; %CD8+Granzime+ T cells in HK-p BDLE= 12 vs 26 HC (p=0.01) vs 10.7 ADLE (p=0.008 vs HC); %CD8+Perforine+ T cells in HK-p BDLE= 8.5 vs 4.8 HC vs 13.2 ADLE; %CD8+Granzime+Perforine+ T cells in HK-p BDLE= 32.8 vs 33.5 HC vs 37.1 ADLE.

Conclusions:: CD8⁺ and CD4⁺ T cells from HK-p predominantly produce IFNγ after treatment with dialyzable leukocyte extract. This increase of cytokine production could explain the better outcomes by a citotoxic T cell response in the studied patients.

Keywords: cornea: clinical science • herpes simplex virus • immunomodulation/immunoregulation