New Treatments: Blocking MCP-1

In November of 2009, a study was conducted by researchers Tominaga, Miyazaki, Sasaki, Mihara, Komatsu, Yakura and Inoue from the Division of Ophthalmology & Visual Science at Tottori University in Japan and published in Investigative Ophthalmology & Visual Science. The study focused on the effects of monocyte chemoattractant protein-1 (MCP 1) in the inflammatory response associated with allergic conjunctivitis. Before delving into the study, let's go into a little more detail regarding allergic reactions.

Allergic reactions can be divided into two categories: Type I immediate-type hypersensitivity or Type 4 delayed-type hypersensitivity (DTH). We are already familiar with Type I, which involves IgE antibodies on mast cells. If you remember, the process of Type I is as follows:

- Allergen enters the body and binds to receptors on a type of white blood cell called a B cell

- B cells digest the allergen and present it to a type of white blood cell called a CD4+ TH2 helper cell

- TH2 cells secrete some mediators that attract other types of white blood cells and other mediators called cytokines IL-4 and IL-5

- IL-4 and IL-5 induce B cells to differentiate into another type of white blood cell called a plasma cell, which then secretes the IgE antibody

- IgE antibodies bind to mast cells

- IgE antibodies are now ready to bind allergen, activating the mast cell to release histamine and other inflammatory mediators

Type 4 or DTH gets its name from the fact that it takes longer (about 1 - 2 days) for this type of allergic reaction to take place, whereas Type I is acute or immediate. DTH involves a type of white blood cell called a macrophage, which basically eats things. In DTH, the macrophage eats the allergen. The process is as follows:

- Attractive mediators secreted by TH2 cells in Type I hypersensitivity recruit other white blood cells, such as macrophages, to the site of the allergen exposure

- Allergen is recognized as foreign by the macrophage, which engulfs it and breaks it up inside

- Macrophage brings those tiny pieces of the allergen to its cell surface and presents it to another type of white blood cell, called a CD4+ TH1 helper cell

- TH1 cells secrete mediators or cytokines called IL2 and IFN γ

- IFN γ stimulates the macrophage to produce a substance called nitric oxide, which produces vasodilation or opening of blood vessels that leads to eye swelling and redness

- IL2 activates another type of white blood cell called a CD8+ cytotoxic T cell (CTL) which essentially kills other cells that have bound the allergen, resulting in eye tissue damage and pain

With all of the different types of white blood cells and cytokines it can get a little confusing, but the take-home message is that an allergic reaction begins with Type I immediate-type hypersensitivity. The longer the allergen stays in the body, the more activated Type I hypersensitivity TH2 cells are and the more likely macrophages will be attracted to the site of the allergen, increasing the chances of a Type 4 DTH.

In the study, the researchers found that injecting mice subjects with MCP-1 caused an allergic reaction, while blocking MCP-1 prevented the allergic reaction. Therefore, MCP-1 must play a key role in causing an allergic reaction. Through further analysis, researchers determined that MCP-1 did not affect IgE antibodies on mast cells at all, which suggests that MCP-1 is necessary for mast cell activation even if IgE binds an allergen. Therefore, blocking MCP-1 may be a new route of therapy for patients with allergic conjunctivitis. Also, blocking MCP-1 prevented Type 4 DTH from occurring after Type I hypersensitivity set in.

The results are interesting and goes to show that we don't know the whole picture for something that seems as simple as allergies. The more things we find are involved with allergic reactions, the more options the pharmaceutical industry has for designing drugs. Maybe the next new drug for allergic conjunctivitis will involve blocking of MCP-1. The fact that more and more mediators are being discovered only gives hope that one day a drug target may be discovered, in which the medication to alter it has an even larger safety profile than what is available today.