Title:  Method of treating systemic inflammatory response syndrome

United States Patent:  6,653,131

Issued:  November 25, 2003

Inventors:  Humes; H. David (Ann Arbor, MI)

Assignee:  The Regents of the University of Michigan (Ann Arbor, MI)

Appl. No.:  941987

Filed:  August 30, 2001

Abstract

A method for treating systemic inflammatory response syndrome (SIRS) by contacting the bodily fluid of a patient with renal tubule cells outside of the kidney.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide methods for treating patients with SIRS.

The present invention is based, in part, on the discovery that a body fluid of a patient with SIRS can be contacted with renal tubule cells outside of the kidney. As a result of this contact, the tubule cells introduce mediators into the body fluid. After contact with the tubule cells, at least a portion of the body fluid is recirculated to the patient, where the mediators induce a response in the patient which leads to amelioration of the SIRS state. As a result of this contact, the tubule cells introduce mediators into and/or reabsorb mediators from the body fluid.

Accordingly, the present invention provides a method of treating a patient with SIRS, comprising:

contacting, outside of the kidney, at least a portion of a body fluid of the patient with renal tubule cells.

The present invention also provides a method of treating a patient with SIRS, comprising:

removing a portion of body fluid from the patient,

contacting the removed body fluid with renal tubule cells, and

returning at least a portion of the body fluid which has been contacted with the renal tubule cells to the patient.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is based, in part, on the inventors' discovery that contacting a body fluid of a patient with SIRS and then returning at least a portion of the treated body fluid to the patient results in amelioration of SIRS. Without being limited to any particular theory, it appears that the cells may provide immunomodulatory effects by influencing systemic cytokine patterns. At the same time, the hemodynamic status of the patient improves as well.

As mentioned above, the patient to be treated according to the present invention has SIRS. In one embodiment, the patient is afflicted with sepsis. In this embodiment, the patient may have been diagnosed with sepsis by a healthcare provider according to diagnostic procedures well-known to those skilled in the art. In another embodiment, the patient has MSOF. Criteria for diagnosing these conditions is described in, for example, Roger C. Bone, in Sepsis and Multiorgan Failure, Alan M. Fein et al., Eds., Williams & Wilkins, Baltimore, Md., 1997, pp. 3-10, incorporated herein by reference.

The patient may be a human or a non-human animal, such as a mammal. Exemplary non-human animals include dogs, cats, horses, cows, sheep, goats, and pigs.

An important feature of the present invention is that the body fluid of the patient is contacted with renal tubule cells. It is important to note that the body fluid of the patient is contacted with renal tubule cells outside of the kidney. In the present invention, the natural flow of the body fluid is interrupted so that the fluid can interact with the renal tubule cells. After this contact, the body fluid is returned to the course of natural flow in the patient's body. Thus, the present invention is distinct from the natural physiological processes which occur in the kidney.

Methods and devices for contacting a body fluid with renal tubule cells and then returning the treated fluid to the patient are well-known in the art. See, for example, references 18, 19, 20, 36, and U.S. Pat. No. 6,150,164, all of which are incorporated herein by reference in their entirety. In a particularly preferred embodiment of the invention, the body fluid of the patient is contacted in with the renal tubule cells in a renal tubule assist device (RAD). As used herein, the term "renal tubule assist device" refers to a device which contains (1) renal tubule cells and (2) an inlet and outlet for the body fluid, where the body fluid is contacted with the renal tubule cells inside the device. Such a device is described in detail in the publications cited immediately above. An example of a suitable RAD is shown in FIG. 1 as element (10) in the a circuit shown therein.

In addition to the methods described in the publications cited immediately above, the renal tubule cells may also be grown on solid or porous microcarrier beads. Examples of suitable microcarrier beads include micropourous gelatin and collagen-coated dextran. In this embodiment, the cells can be grown on the beads. Then, the cells can be detached from the beads and be seeded in the RAD. In another embodiment, the cells on the beads can be used in the extracapillary space of a sepsis treating cartridge on microcarrier beads as opposed to single monolayers along the inner surface of hollow fibers. Thus, a body fluid of a patient could be perfused into a cartridge containing these cells in this formulation for exposure to the patient's fluid and respond with mediators that would alter the SIRS condition.

The tubule cells may be obtained from a human or a non-human animal source. The non-human animal is preferably a mammal. Suitable examples of non-human cells are porcine, rat, dog, mouse, or rabbit tubule cells. Transformed tubule cells may also be used in the present invention. Such cells are described in, for example, U.S. Pat. No. 6,150,164.

The body fluid may be blood, plasma, or ultrafiltrate of plasma. Venous blood is particularly preferred. Arterial blood may also be used.

In one embodiment of the invention, the body fluid of the patient is contacted in with the renal tubule cells ex vivo, i.e, outside of the body of the patient. In an alternative embodiment, the body fluid is contacted in with the renal tubule cells inside the body of the patient.

In one embodiment, the renal tubule assist device is ex vivo. Alternatively, the renal tubule assist device is implanted in the patient.

Claim 1 of 23 Claims

What is claimed is:

1. A method of treating a patient with SIRS syndrome, comprising:

contacting, outside of the kidney, at least a portion of the body fluid of the patient with renal tubule cells.

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