Device and method for inhibiting release of pro-inflammatory mediator

Abstract

Stimulation of one or more neurons of the sympathetic nervous system, including the splenic nerve, to attenuate an immune response, including an inflammatory immune response, is discussed. Devices and systems to stimulate the sympathetic nervous system to attenuate an immune response are also discussed. Devices discussed include pulse generators and drug pumps. Systems are described as optionally having one or more sensors and operator instructions. In specific examples, stimulation of the splenic nerve of pigs with a pulse generator is shown to be safe and effective in attenuating a lipopolysaccharide-induced immune response.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Application No. 60 / 507,855, filed Oct. 1, 2003, which provisional application is hereby incorporated herein by reference in its entirety.FIELD OF THE INVENTION [0002] The invention relates to medical devices and methods for modulating neurons and modulating an immune response. BACKGROUND [0003] The use of electrical stimulation to attenuate an immune response has only recently been described and has been limited to stimulation of a parasympathetic nerve. U.S. Pat. No. 6,610,713 (Tracey) demonstrated that stimulation of the parasympathetic vagus nerve prior to bacterial challenge resulted in a weakened systemic inflammatory response and was associated with greater survivability. [0004] While intriguing, stimulation of the vagus nerve to attenuate an immune response presents several concerns. Because the vagus nerve is comprised predominantly of afferent fibers, stimulation of the vagus...

AI Technical Summary

Benefits of technology

[0014] The invention can provide a number of advantages. For example, by stimulating the sympathetic nervous system, which innervates all primary and secondary lymphoid organs, the invention provides for great flexibility for controlling an inflammatory immune response. By stimulating one or more sympathetic nerves that innervate one or more lymphoid organs, an inflammatory immune response can be attenuated at one or more levels. In addition, the invention provides for greater specificity with reduced potential undesired, non-specific effects. For example, stimulating the splenic nerve, which is comprised primarily of efferent fibers, can attenuate an immune response while minimizing direct CNS effects due to the stimulation. Other advantages will also be evident based on the disclosure herein.

Problems solved by technology

The use of electrical stimulation to attenuate an immune response has only recently been described and has been limited to stimulation of a parasympathetic nerve.

Because the vagus nerve is comprised predominantly of afferent fibers, stimulation of the vagus nerve can produce undesired, non-specific CNS effects.

While U.S. Pat. No. 6,610,713 discusses selective stimulation of the efferent vagus, selective efferent stimulation will be difficult to achieve in a predominantly afferent nerve such as the vagus.

Accordingly, stimulation of the vagus nerve to attenuate an immune response may result in many undesired and non-specific effects.

Further, due to the complex mechanisms underlying control of an immune response, stimulation of the vagus nerve may not produce a complete or effective attenuation of a systemic inflammatory response.

Dysfunction of these cell types can lead to increased release of pro-inflammatory cytokines resulting in inflammation and an excessive immune response.

Similarly, dysfunction in these cell types can lead to a suppressed immune response such as that observed in immunocompromised patients.

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