Methods for suppressing Toll-like Receptor 4 (TLR4) function using TLR14 antagonists

1. A method for suppressing Toll-like Receptor 4 (TLR4))-mediated inflammation, the method comprising:

administering, to a subject in need of suppression of TLR4-mediated inflammation, an inhibitory antibody against a Toll-like Receptor 14 (TLR14) protein, or an antigen binding fragment thereof, said TLR14 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein the antibody or antigen binding fragment thereof:

(i) belongs to a subclass chosen from IgG1, IgG2a, IgG2b, IgG3, or IgG4; and

(ii) is administered in an amount sufficient to suppress TLR4-mediated inflammation.

2. The method as claimed in claim 1 , wherein the antibody or antigen binding fragment thereof inhibits activation of NF-KB, interferon regulated factor 3, mitogen-activated protein kinase (MAPK), p38, c-jun N-terminal kinase (JNK) or p42/44.

3. The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, is a chimeric, CDR-grafted, humanized or chimeric antibody.

4. The method of claim 1 , wherein the antigen binding fragment thereof is an Fab, an F(ab′)2, an fv or a scFv.

5. The method of claim 1 , wherein the subject is a human.

6. A method for the treatment of septicaemia or septic shock, the method comprising:

administering, to a subject in need thereof, an antibody against a Toll-like Receptor 14 (TLR14) protein, or an antigen binding fragment thereof, said TLR14protein comprising the amino acid sequence of SEQ ID NO:1, wherein the antibody or antigen binding fragment thereof is administered in an amount sufficient to treat the septicaemia or septic shock, and

wherein the antibody belongs to a subclass chosen from IgG1, IgG2a, IgG2b, IgG3, or IgG4.

7. The method as claimed in claim 6 , further comprising the step of administering to the subject a composition which inhibits the expression or biological function of CD14, wherein the composition is chosen from a CD14 inhibitory nucleic acid, a soluble form of CD14, a peptide CD14 inhibitor compound, a CD14fusion protein, or an antibody against CD14.

8. The method as claimed in claim 6 , wherein the antibody or antigen binding fragment thereof inhibits an association of Toll-like Receptor 14 with Toll-like Receptor 4.

9. The method of claim 6 , wherein the antibody, or antigen binding fragment thereof, is a chimeric, CDR-grafted, humanized or chimeric antibody.

10. A method for suppressing Toll-like Receptor 4 (TLR4)-mediated inflammatory activation and signaling, the method comprising:

contacting a cell expressing a Toll-like Receptor 14 (TLR14) protein and a TLR4protein with an antibody against the TLR14 protein, or an antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof:

(i) belongs to a subclass chosen from IgG1, IgG2a, IgG2b, IgG3, or IgG4, and

(ii) is in an amount sufficient to inhibit a biological function of TLR14, and

wherein the biological function of TLR14 results in the TLR4-mediated inflammatory activation and signaling, thereby suppressing TLR4-mediated inflammatory activation and signaling.

11. The method of claim 10 , wherein the antibody or antigen binding fragment thereof inhibits an association of TLR14 with TLR4.

12. The method of claim 10 , wherein the TLR14 protein comprises the amino acid sequence of SEQ ID NO:1.

13. The method of claim 10 , wherein the antibody, or antigen binding fragment thereof, is a chimeric, CDR-grafted, humanized or chimeric antibody.

14. The method of claim 10 , wherein the antigen binding fragment thereof is an Fab, an F(ab′)2, an Fv or a scFv.

15. The method of claim 10 , wherein the contacting step occurs in vitro.