To investigate potential immunologic mechanisms of resistance to recur
rent herpes simplex labialis, we assayed serum antibody titers and cul
tured peripheral blood mononuclear cell (PBMC) cytokine production amo
ng patients with a history of frequent episodes (H+S+), herpes simplex
virus (HSV)-seropositive individuals without a history of herpes labi
alis (H-S+) and HSV-seronegative persons (H-S-). In addition, H+S+ pat
ients were exposed to experimental ultraviolet radiation (UVR) on the
lips and the immunologic assay results compared among those who develo
ped experimental lesions and those who did not. H+S+ patients were fou
nd to have higher median serum titers of HSV antibody and trends to lo
wer levels of HSV-specific PBMC IFN-gamma and IL-2 than H-S+ control p
atients (123 vs 66, P = 0.04; 424 vs 548 pg/ml, P = 0.08; 14 vs 26 pg/
ml, P = 0.14, respectively). Correlation of the results with the occur
rence of experimental lesions showed the inverse: the subgroup of H+S patients with UVR-induced lesions had lower titers of antibody and tr
ends to higher levels of IFN-gamma and IL-2 than H+S+ patients who cou
ld not be induced (93 vs 149, P = 0.02; 501 vs 347 pg/ml, P = NS; 26 v
s 11 pg/ml, P = NS, respectively). The size and duration of UVR-induce
d lesions showed positive correlations with IFN-gamma and IL-2 levels
(r = 0.60-0.67, P = 0.02-0.04). Although the small number of patients
limited the power of this study, the overall pattern of the findings s
uggests that a Th1-like cytokine response (IFN-gamma and IL-2 producti
on) may be associated with resistance to naturally occurring episodes
of herpes labialis. The development and severity of experimental UVR-i
nduced herpes labialis appears to be regulated differently and may inv
olve an immunopathologic mechanism.