(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date \ r /n rn n 2 February 2012 (02.02.2012) / A (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every CI2Q 1/68 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (21) International Application Number: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, PCT/US201 1/045705 DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, 28 July 201 1 (28.07.201 1) KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (25) Filing Language: English NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (26) Publication Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/368,532 28 July 2010 (28.07.2010) US (84) Designated States (unless otherwise indicated, for every 61/432,387 13 January 201 1 (13.01 .201 1) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, (71) Applicant (for all designated States except US): UNI¬ ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, VERSITY OF MEDICINE AND DENTISTRY OF TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, NEW JERSEY [US/US]; 1 World's Fair Drive, Somer EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, set, NJ 08873 (US). LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, (72) Inventors; and GW, ML, MR, NE, SN, TD, TG). (75) Inventors/ Applicants (for US only): LOWRY, Stephen, F. [US/US]; 1 World's Fair Drive (US). HAIMOVICH, Published: Beatrice [US/US]; 1 World's Fair Drive (US). RED- — without international search report and to be republished DELL, Michael [US/US]; 1 World's Fair Drive (US). upon receipt of that report (Rule 48.2(g)) (74) Agents: BUTCH, Peter, J., Ill et al; FOX ROTH SCHILD LLP, 997 Lenox Drive, Building 3, Lawrenceville, NJ 08648-23 11 (US). < © o © o (54) Title: INFLAMMATION DETECTION (57) Abstract: The present invention relates to methods and reagents for detecting and monitoring inflammation and injury in a subject by determining the expression levels of groups of genes. INFLAMMATION DETECTION CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority of U.S. Provisional Application No. 61/432,387, filed on January 13, 2011, and U.S. Provisional Application No. 61/368,532, filed on July 28, 2010. The contents of the applications are incorporated herein by reference in their entireties. GOVERNMENT INTERESTS The invention disclosed herein was made, at least in part, with Government support under Grant No. NIH GM 34695 from the National Institutes of Health. Accordingly, the U.S. Government has certain rights in this invention. FIELD OF THE INVENTION This invention relates to reagents and methods for detecting inflammation in a subject. BACKGROUND OF THE INVENTION Inflammation is a complex biological response of the body to harmful stimuli, such as pathogens, damaged cells, or irritants. It is involved in various inflammatory disorders. Inflammatory disorders, characterized by the abnormal activation and subsequent migration of leukocytes or white blood cells to affected areas of the body, encompass a wide range of ailments that affect the lives of millions of people throughout the world. Few tests exist that reliably diagnose or monitor the progress of inflammation and the disorders. Thus, there is a need for reagents and methods for detecting inflammation. Circulating leukocytes play a central role in host immunity, and are a major source of inflammatory mediators released in response to exposure to pathogen-associated molecular pattern(s) (PAMPs), such as endotoxin. Gene expression profiling of human peripheral blood leukocytes (PBL) or mononuclear cells have revealed robust gene expression changes that are detectable within 2 hours of an in vivo endotoxin challenge. The acute phase of systemic inflammation is associated with the release of numerous cytokines and inflammatory mediators, as well as global changes in gene expression in PBL. Yet, changes in cytokines are significantly less robust, and hence difficult to establish, during conditions of low-grade inflammation. Thus, there also remains a need for an improved method of identifying the presence of inflammation and for monitoring a patient' s response. SUMMARY OF INVENTION This invention is based, at least in part, on the unexpected discovery of a group of genes that exhibit similar expression trends in PBL derived from trauma patients and from subjects challenged with endotoxin, which induced acute inflammation via the Toll-like receptor4 (TLR4) pathway. As disclosed herein, the TLR4-induced transcription patterns elicited in humans exposed to endotoxin parallel gene expression patterns observed in trauma patients with initial non-infectious injury. Accordingly, in one aspect, this invention features a method for determining whether a subject has, or is at risk of having, an inflammatory disorder, e.g., sepsis or a systemic inflammatory response syndrome. The method includes, among others, steps of obtaining from the subject a sample and determining in the sample the expression levels of a plurality of genes. Each of the genes is selected from (i) a first panel of up-regulated TLR4 and Injury Responsive (TIR) genes, (ii) a second panel of down-regulated TIR genes, or (iii) a third panel of core genes. The subject is determined to have, or to be at risk of having, the disorder if: (a) the expression level of each gene selected from the first panel is above a first predetermined reference value; (b) the expression level of each gene selected from the second panel is below a second predetermined reference value; or (c) the expression level of each gene selected from the third panel is below a third predetermined reference value. The sample can be a blood sample or any other suitable sample that contains leukocytes. The first, second, or third predetermined reference value can be obtained from a control subject that does not have the disorder. The afore-mentioned "TLR4 and Injury Responsive (TIR) genes" refers to genes that exhibit persisted differential expression (i.e., up-regulated or down-regulated) in response to TLR4-induced systemic inflammation and/or injury, which can be determined by the method described in Examples 1 and 2 below. This group of genes includes the 449 genes listed in Table 3. These 449 genes include (a) a first panel of 176 up-regulated TIR genes whose expression levels in a healthy subject increase (i.e., up-regulated) in response to an endotoxin challenge and (b) a second panel of 273 down-regulated TIR genes whose expression levels in a healthy subject decrease (i.e., done-regulated) in response to an endotoxin challenge. In one embodiment, each gene for practicing the above-described method is selected from the third panel of core genes. This panel of core genes can include the Cryl, Cry2, Per3, Clock, Rora, Rev, CSNKle, and CDK4 genes. In one example, this panel consists of the Cryl, Cryl, Per , Clock, Rora, Rev, CSNKle, and CDK4 genes. In a second aspect, the invention features a method for determining a prognosis of an inflammatory disorder (e.g., sepsis or a systemic inflammatory response syndrome) in a subject that has received an injury. The method includes, among others, steps for obtaining from the subject a sample and for determining in the sample the magnitude of a change in the expression level of one or more genes. Each of the genes is selected from (i) the first panel of up-regulated TIR genes, (ii) the second panel of down-regulated TIR genes, (iii) the third panel of core genes, or (iv) a fourth panel of reversible responsive genes. The "reversible responsive genes" refers to a panel of genes that show differential expression in response to TLR4- induced systemic inflammation and/or injury, but reverse their expression trends within a period of time, such as 9-12 days. Examples of these genes include the 150 genes listed in Table 4. The just-mentioned magnitude (i.e., extent or degree) of the change is indicative of the prognosis of the subject. The prognosis method can further include a step of comparing the magnitude to a predetermined magnitude reference value whereby the subject is determined to have a good prognosis if the magnitude is below the predetermined reference value. The predetermined magnitude reference value can be obtained from a patient that has the disorder. Alternatively, it can be obtained from the subject at a time after receiving the injury, but before the above- mentioned sample is obtained. In other words, a decrease in the magnitude over time indicates a good prognosis. The sample can be a blood sample or any other suitable sample that contains leukocytes. In one embodiment, the one or more genes for practicing the prognosis method are selected from the fourth panel. In one example, the sample can be obtained from the subject within 12 days after receiving the injury or after the onset of the disorder. Preferably, the sample is obtained from the subject within, e.g., 9-12 days after receiving the injury or after the onset of the disorder.