T-HELPER-CELL CYTOKINES IN THE EARLY EVOLUTION OF MURINE LYME ARTHRITIS

Genetic susceptibility to murine Lyme arthritis has been correlated wi th the dominance of T-helper (Th1)- or Th2-cell-associated cytokines, To determine when commitment of the Th cell phenotype occurs, we exami ned the kinetics of gamma interferon (IFN-gamma) and interleukin-4 (IL -4) production by lymph node T cells of disease-susceptible C3H/HeN an d disease-resistant BALB/c mice from days 2 through 30 of infection, a period encompassing the evolution of disease and early regression, BA LB/c mice produced more IFN-gamma on day 2 of infection than did C3H/H eN mice, whereas IL-4 was first detected on day 14, In contrast, only IFN-gamma could be detected in C3H/HeN mice, and the levels steadily i ncreased from day 2 to surpass those seen in BALB/c mice by day 14 of infection. Despite the difference in cytokine profiles, both BALB/c an d C3H/HeN mice developed comparable arthritis assessed at 14 days of i nfection, Arthritis regressed by day 30 in BALB/c mice but persisted i n C3H/HeN mice. These studies are the first to demonstrate that the Th 2 response to Borrelia burgdorferi infection of BALB/c mice is precede d by a Thl cytokine response, Moreover, the timing of the appearance o f IL-4 suggests that its primary effect is not in preventing disease, as suggested by others, but, rather, in hastening the resolution of in flammation, The implications of these findings for the orchestration o f host defense against B, burgdorferi infection are discussed.