A method for stimulating production of a pro-inflammatory cytokine selected from TNF-alpha and IL-12 comprising: contacting a TLR8 expressing cell in vitro with an RNA oligonucleotide comprising: N-U-R 1 -R 2, wherein N is a ribonucleotide and N does not include a U, U is Uracil or a derivative thereof, and R is a ribonucleotide wherein at least one of R 1 and R 2 is Adenosine or Cytosine or derivatives thereof and wherein R is not U unless N-U-R 1 -R 2 includes at least two A, wherein the ORN is selected from: GCCACCGAGCCGAAUAUACC SEQ ID NO: 11; AUAUAUAUAUAUAUAUAUAU SEQ ID NO:12; UUAUUAUUAUUAUUAUUAUU SEQ ID NO:13; AAUAAUAAUAAUAAUAAUAA SEQ ID NO:16; AAAUAAAUAAAUAAAUAAAU SEQ ID NO: 17; AAAAUAAAAUAAAAUAAAAU SEQ ID NO:18; CUACUACUACUACUACUACU SEQ ID NO:24; UUAUUAU SEQ ID NO:30; UAUAUAU SEQ ID NO:33; CCGAGCCGCAUAUCCC SEQ ID NO:36; CCGAGCCGCUAUACCC SEQ ID NO:37; CCGAGCCAUAUAUCCC SEQ ID NO:38; CCGAGCCAUAUAUAUC SEQ ID NO:39; CCGAGCCGAAUAACCC SEQ ID NO:40; CCGAGCCGCAUAACCC SEQ ID NO:41; CCGAGCCGAAUACCCC SEQ ID NO:42; CCGAGCCGCCUAACCC SEQ ID NO:43; CCGAGCCGAAUCCCCC SEQ ID NO:44; CCGAGCCGCAUACCCC SEQ ID NO:45; CCGAGCCGCAUCCCCC SEQ ID NO:46; CCGAGCCGCCUACCCC SEQ ID NO:47; CCGAGCCGCAUUACCC SEQ ID NO:48; CCGAGCCGCUAUCCCC SEQ ID NO:55; CCGAGCCGAAUGUACC SEQ ID NO:63; CCGAGCCGAUAUUACC SEQ ID NO:65; CCGAGCCGAAGGUACC SEQ ID NO:82; CCGAGCCGAAGGUGCC SEQ ID NO:83; CCGAGCCGAAGCUCCC SEQ ID NO:84; CCGAGCCGAAGAUACC SEQ ID NO:85; CCGAGCCGAAGCUACC SEQ ID NO:87; and CCGAGCCGAAGCUGCC SEQ ID NO:88; wherein the ORN optionally includes at least one backbone modification; in an effective amount to stimulate pro-inflammatory cytokine production and wherein IFN-α production in response to the ORN is not induced significantly relative to background; and further wherein the ORN is complexed to N-[1-(2,3-Dioleoyloxy)propyl]-N,N,Ntrimethylammoniummethyl-sulfate (DOTAP). contacting a TLR8 expressing cell in vitro with an RNA oligonucleotide comprising: N-U-R 1 -R 2, wherein N is a ribonucleotide and N does not include a U, U is Uracil or a derivative thereof, and R is a ribonucleotide wherein at least one of R 1 and R 2 is Adenosine or Cytosine or derivatives thereof and wherein R is not U unless N-U-R 1 -R 2 includes at least two A, wherein the ORN is selected from: GCCACCGAGCCGAAUAUACC SEQ ID NO: 11; AUAUAUAUAUAUAUAUAUAU SEQ ID NO:12; UUAUUAUUAUUAUUAUUAUU SEQ ID NO:13; AAUAAUAAUAAUAAUAAUAA SEQ ID NO:16; AAAUAAAUAAAUAAAUAAAU SEQ ID NO: 17; AAAAUAAAAUAAAAUAAAAU SEQ ID NO:18; CUACUACUACUACUACUACU SEQ ID NO:24; UUAUUAU SEQ ID NO:30; UAUAUAU SEQ ID NO:33; CCGAGCCGCAUAUCCC SEQ ID NO:36; CCGAGCCGCUAUACCC SEQ ID NO:37; CCGAGCCAUAUAUCCC SEQ ID NO:38; CCGAGCCAUAUAUAUC SEQ ID NO:39; CCGAGCCGAAUAACCC SEQ ID NO:40; CCGAGCCGCAUAACCC SEQ ID NO:41; CCGAGCCGAAUACCCC SEQ ID NO:42; CCGAGCCGCCUAACCC SEQ ID NO:43; CCGAGCCGAAUCCCCC SEQ ID NO:44; CCGAGCCGCAUACCCC SEQ ID NO:45; CCGAGCCGCAUCCCCC SEQ ID NO:46; CCGAGCCGCCUACCCC SEQ ID NO:47; CCGAGCCGCAUUACCC SEQ ID NO:48; CCGAGCCGCUAUCCCC SEQ ID NO:55; CCGAGCCGAAUGUACC SEQ ID NO:63; CCGAGCCGAUAUUACC SEQ ID NO:65; CCGAGCCGAAGGUACC SEQ ID NO:82; CCGAGCCGAAGGUGCC SEQ ID NO:83; CCGAGCCGAAGCUCCC SEQ ID NO:84; CCGAGCCGAAGAUACC SEQ ID NO:85; CCGAGCCGAAGCUACC SEQ ID NO:87; and CCGAGCCGAAGCUGCC SEQ ID NO:88; wherein the ORN optionally includes at least one backbone modification; GCCACCGAGCCGAAUAUACC SEQ ID NO: 11; AUAUAUAUAUAUAUAUAUAU SEQ ID NO:12; UUAUUAUUAUUAUUAUUAUU SEQ ID NO:13; AAUAAUAAUAAUAAUAAUAA SEQ ID NO:16; AAAUAAAUAAAUAAAUAAAU SEQ ID NO: 17; AAAAUAAAAUAAAAUAAAAU SEQ ID NO:18; CUACUACUACUACUACUACU SEQ ID NO:24; UUAUUAU SEQ ID NO:30; UAUAUAU SEQ ID NO:33; CCGAGCCGCAUAUCCC SEQ ID NO:36; CCGAGCCGCUAUACCC SEQ ID NO:37; CCGAGCCAUAUAUCCC SEQ ID NO:38; CCGAGCCAUAUAUAUC SEQ ID NO:39; CCGAGCCGAAUAACCC SEQ ID NO:40; CCGAGCCGCAUAACCC SEQ ID NO:41; CCGAGCCGAAUACCCC SEQ ID NO:42; CCGAGCCGCCUAACCC SEQ ID NO:43; CCGAGCCGAAUCCCCC SEQ ID NO:44; CCGAGCCGCAUACCCC SEQ ID NO:45; CCGAGCCGCAUCCCCC SEQ ID NO:46; CCGAGCCGCCUACCCC SEQ ID NO:47; CCGAGCCGCAUUACCC SEQ ID NO:48; CCGAGCCGCUAUCCCC SEQ ID NO:55; CCGAGCCGAAUGUACC SEQ ID NO:63; CCGAGCCGAUAUUACC SEQ ID NO:65; CCGAGCCGAAGGUACC SEQ ID NO:82; CCGAGCCGAAGGUGCC SEQ ID NO:83; CCGAGCCGAAGCUCCC SEQ ID NO:84; CCGAGCCGAAGAUACC SEQ ID NO:85; CCGAGCCGAAGCUACC SEQ ID NO:87; and CCGAGCCGAAGCUGCC SEQ ID NO:88; wherein the ORN optionally includes at least one backbone modification; in an effective amount to stimulate pro-inflammatory cytokine production and wherein IFN-α production in response to the ORN is not induced significantly relative to background; and further wherein the ORN is complexed to N-[1-(2,3-Dioleoyloxy)propyl]-N,N,Ntrimethylammoniummethyl-sulfate (DOTAP).