Differential modulation of allergic eye disease by chronic and acute ascaris infection.

PURPOSE: To assess alterations in allergic ocular responses to nonparasite antigens in an experimental system in which mice were skewed toward a Th2 cytokine profile by helminth infection. METHODS: Mice were inoculated with Ascaris suum (A. suum) eggs concurrent with ragweed (RW) sensitization (RW/acute) or by repeated inoculation before RW sensitization (RW/chronic). Control subjects were divided into RW, A. suum, and sham-sensitized groups. Animals were RW-challenged in the eye and examined for changes in ocular responses, inflammatory cell infiltrates, and in vitro assessment of cytokines after antigen restimulation. In subsequent experiments, CD4(+)/CD25+ T regulatory and CD4(+)/CD25- control T cells were adoptively transferred into mice before ocular challenge. RESULTS: RW sensitization and challenge increased ocular symptoms and eosinophil infiltration into the conjunctiva over PBS control eyes. Acute A. suum infection significantly increased RW-induced clinical symptoms and eosinophil infiltrates in the conjunctiva (P = 0.0001) and resulted in the development of anterior uveitis. In contrast, RW/chronic infection provided protection from allergic responses to RW with significantly fewer eosinophils in the eye and reduced eotaxin levels. Transfer of CD4(+)/CD25+ T cells from RW/chronic mice into RW/acute animals also decreased disease intensity, suggesting that T regulatory cells may contribute to protection from allergic eye disease. CONCLUSIONS: The current studies suggest acute parasitic infections exacerbate allergic symptoms, whereas chronic infections offer protection and provide possible explanations for the role of parasitic infection in susceptibility and resistance to nonparasite allergens.

Pharmacy benefit management contracting: an assessment from a recent public sector procurement experience.

In order to contain the cost of pharmaceuticals while preserving access to medically necessary drugs, Georgia state government competitively selected a single vendor in May of 2000 to manage combined pharmacy benefits under all of the state's health programs. By initiating this procedure, it intended to maximize the state's purchasing power and improve efficiency while streamlining the administrative structure. Synthesizing information from the request for proposal (RFP) and technical proposals submitted by 11 pharmacy benefit managers (PBMs) in response, we describe a model of public sector PBM contracting approach and present an assessment of the industry's service capability and performance statistics. Payers who have been using PBM services may find it interesting to compare their experience with the recent Georgia experience. Those who are considering contracting with a PBM will find the assessment of the PBM industry timely and informative.

Gq signaling is required for allergen-induced pulmonary eosinophilia.

The complexity and magnitude of interactions leading to the selective infiltration of eosinophils in response to inhaled allergens are formidable obstacles to a larger understanding of the pulmonary pathology associated with allergic asthma. This study uses knockout mice to demonstrate a novel function for the heterotrimeric G protein, G(q), in the regulation of pulmonary eosinophil recruitment. In the absence of G(q) signaling, eosinophils failed to accumulate in the lungs following allergen challenge. These studies demonstrate that the inhibition of eosinophil accumulation in the airways is attributed to the failure of hemopoietically derived cells to elaborate GM-CSF in the airways. The data suggest that activation of a G(q)-coupled receptor(s) on resident leukocytes in the lung elicits expression of GM-CSF, which, in turn, is required for allergen-induced pulmonary eosinophilia, identifying a novel pathway of eosinophil-associated effector functions leading to pulmonary pathology in diseases such as asthma.