Isolated complexes of endotoxin and modified MD-2

1. A purified complex comprising endotoxin bound to a modified human MD-2, wherein the modified human MD-2 comprises a variation from wild-type human MD-2 at amino acid 68, 69, 126, 127, 128, 129, 130, and/or 131, wherein the complex inhibits TLR4-dependent activation of cells.

2. The complex of claim 1 , wherein the variation is an amino acid substitution.

3. The complex of claim 2 , wherein the substitution is a conserved substitution.

4. The complex of claim 2 , wherein the substitution is an alanine.

5. The complex of claim 1 , wherein the endotoxin is a wild-type endotoxin.

6. The complex of claim 1 , wherein the endotoxin is a gram-negative bacterial endotoxin.

7. The complex of claim 1 , wherein one molecule of endotoxin is bound to one molecule of MD-2.

8. The complex of claim 1 , wherein the complex is soluble in water.

9. The complex of claim 1 , wherein the complex binds to TLR4.

10. The complex of claim 1 , wherein the complex inhibits TLR4-dependent activation of cells by endotoxin or by monomeric complexes of endotoxin-bound wild-type human MD-2.

11. The complex of claim 10 , wherein the complex produces a half maximal TLR4-dependent inhibition of cells by endotoxin or by monomeric complexes of endotoxin-bound wild-type human MD-2 at a concentration of less than 1 nM of the complex.

12. The complex of claim 10 , wherein the complex produces a half maximal TLR4-dependent inhibition of cells by endotoxin or by monomeric complexes of endotoxin-bound wild-type human MD-2 at a concentration of about 30 pM or less of the complex.

13. The complex of claim 1 , wherein the endotoxin is hexa-acylated.

14. The complex of claim 1 , wherein the endotoxin is an under-acylated endotoxin.

15. The complex of claim 14 , wherein the endotoxin is a tetra-acylated endotoxin.

16. The complex of claim 14 , wherein the endotoxin is a penta-acylated endotoxin.

17. The complex of claim 1 , wherein the complex produces less TLR4-dependent activation of cells as compared to a complex comprising an endotoxin that is hexa-acylated.

18. A composition comprising the complex of claim 1 .

19. The composition of claim 18 , further comprising a pharmaceutically acceptable carrier.