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Effect of cyclophosphamide on primary herpes simplex uveitis in rabbits.

Intracameral injection of the normal rabbit eye with 10 50% tissue culture infectious doses of type 1 herpes simplex virus (HSV) caused uveal inflammation, biphasic elevation of intraocular pressure (IOP), and virus growth in the ocular tissues. A series of intramuscular injections of an immunosuppressive agent, cyclophosphamide (Cy), did not affect the ocular changes or the multiplication of virus in the uveal tissues in the early stage of the disease (days 1 to 6). During this period neither circulating antibody nor macrophage migration inhibition factor (MIF) against HSV appeared in either control or Cy-treated animals, suggesting that the disease is initiated by infectious processes. After day 7, however, virus growth in the uveal tissues of the Cy-treated animals was much more abundant and more prolonged than in the tissues of the control eyes, but uveal inflammation in the Cy-treated animals was much milder and subsided earlier than in the control animals. The Cy treatment suppressed completely the second rise of IOP which normally appears on day 7. These effects of Cy in the late period coincided with a significant suppression of both circulating antibody and MIF, indicating that the late stage of the uveitis was mediated by immune mechanisms. We conclude therefore that primary herpes simplex uveitis in the rabbit is dually mediated, first by the mechanisms of infection and later by the mechanisms of immunity.