Mechanisms by which Retrobulbar Fibroblasts are Stimulated by Lymphocytes: Role of Cyclic Nucleotide

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Abstract
[The increased synthesis of hyaluronic acid (HA) by cultured cells from the human orbit may provide an analogy to Graves'' ophthalmopathyl.] Lymphocytes and lymphocyte products stimulated HA synthesis in cultures of human retrobulbar fibroblasts. This stimulation was simulated by dibutyryl cyclic AMP (DbcAMP), 2 .times. 10-4-10-2 M, and potentiated by theophylline, 10-4 M. Lymphocytes induced a significant increase in the cAMP concentration within the fibroblasts. These data support the concept that the lymphocyte stimulation of HA synthesis is mediated by cAMP. Lymphocytes induced greater glucose utilization by the cultures than DbcAMP. The intrinsic viscosity of the HA was decreased by lymphocytes but increased by DbcAMP. lymphocytes probably produce more effects in the fibroblasts than those mediated by cAMP. Hydrocortisone inhibited both the cAMP and the HA responses to lymphocytes but potentiated the stimulation of HA synthesis by DbcAMP. Hydrocortisone thus appears to interfere with the earliest effects of lymphocytes, possibly inhibiting the binding of the active factor in lymphocytes to retrobulbar fibroblasts.

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