NEBULIZED IFN-GAMMA INHIBITS THE DEVELOPMENT OF SECONDARY ALLERGIC RESPONSES IN MICE

The effects of nebulized IFN-gamma on primary and secondary IgE produc tion and development of airway hyper-responsiveness (AHR) were investi gated. BALB/c mice received primary exposure to aerosolized OVA daily for 10 days and developed anti-OVA IgE responses, immediate cutaneous reactivity to OVA, and altered airway function when assayed on day 12. After secondary exposure to OVA challenges on days 30 and 31, these m ice developed an amplified IgE response, heightened cutaneous reactivi ty to OVA and AHR when measured on day 37. Administration of IFN-gamma for 13 days, beginning 3 days prior to and during primary OVA sensiti zation, resulted in a decrease in anti-OVA IgE, increases in serum ant i-OVA IgG2a levels, a decrease in cutaneous reactivity to OVA, and nor mal airway function when assessed on day 12 after primary sensitizatio n, This treatment also prevented the development of secondary anti-OVA IgE responses and altered airway responsiveness but did not induce a secondary rise in anti-OVA IgG2a in the serum measured on day 37. Trea tment with IFN-gamma on days 26 to 30, well after primary responses we re established but just prior to secondary OVA challenge, abolished th e development of secondary anti-OVA IgE responses, resulted in an incr ease in anti-OVA IgG2a in the serum, and prevented the development of AHR. In vitro, CD4(+) T cells obtained from OVA-sensitized mice treate d with either ''early'' or ''late'' IFN-gamma inhibited IgE production . Delivery of IFN-gamma to the airways can prevent secondary allergen sensitization even after primary sensitization has been achieved and t his effect is mediated by CD4(+) T cells.